Devices containing cell membranes and uses thereof

Abstract

The present disclosure relates to a device, e.g., an extracorporeal blood purification (EBP) device, that includes a cartridge or adsorbent containing cell membranes derived from cells. The present disclosure also relates to a method for removing or reducing substances (e.g., unwanted substances) from a fluid (e.g., a subject's blood) using the device or EBP device. In another aspect, the present disclosure provides a device assembly that includes at least two of the devices or EBP devices that are in fluid communication.

Description

[Technical field]

[0001] I. Related Applications This application claims priority to U.S. Provisional Patent Application No. 62 / 963,465, filed January 20, 2020, the disclosure and contents of which are incorporated by reference in their entirety for all purposes.

[0002] II. FIELD OF THEINVENTION The present disclosure relates to devices (e.g., extracorporeal blood purification (EBP) devices) that include cartridges or sorbents that include cell-derived membranes. The present disclosure also relates to methods for removing or reducing substances (e.g., unwanted substances) from a fluid (e.g., a subject's blood) using the devices or EBP devices. [Background technology]

[0003] III. Background of the Invention Extracorporeal blood purification (EBP) is a treatment procedure in which a patient's blood is allowed to pass through a device for removal of unwanted solutes (e.g., waste products, proinflammatory cytokines, and toxins). The devices used for EBP can be divided into two major categories: (1) filtration based on molecular size (e.g., hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), and high-flux dialysis (HFD)), and (2) adsorption (e.g., devices based on nonspecific physical interactions or specific ligand-receptor binding interactions). Due to its convenience and low risk of complications, EBP has been used to treat serious diseases (e.g., renal failure, liver failure, and sepsis).

[0004] However, existing technologies face significant drawbacks. (1) Devices based on filtration, convection, and diffusion use molecular weight as a cutoff and cannot distinguish what the filtrate is biologically. (2) Convection and diffusion cannot achieve good clinical clearance of high molecular weight and hydrophobic molecules because the volume of the injectate is limited in convection and the membrane permeability is limited in diffusion. (3) Devices based on physical adsorption (e.g., charcoal) are non-specific and are harmful by removing even extremely important molecules non-differentially. (4) Regarding specific adsorption, the selection of ligands that bind to toxins is limited and costly. For each target toxin, its ligand needs to be specifically generated, which is impractical for diseases where most pathological or pathogenic factors are unknown.

[0005] There is a need for a novel device or EBP device, and a method for removing or reducing substances (e.g., unwanted substances) from a subject's fluid or blood using the above device or EBP device to address the problems of current devices and methods. The present invention addresses this and related needs in the art.

Summary of the Invention

Means for Solving the Problems

[0006] IV. Gist of the Invention In one aspect, the present disclosure provides a device (e.g., an extracorporeal blood purification (EBP) device) comprising a cartridge or adsorbent comprising a cell membrane derived from a cell.

[0007] In another aspect, the present disclosure provides a device assembly comprising at least two of the above devices or EBP devices in fluid communication. The devices or EBP devices in the device assembly comprise cartridges or adsorbents comprising cell membranes derived from different cell types.

[0008] In yet another aspect, the disclosure provides a method for removing or reducing a substance (e.g., an unwanted substance) from a fluid (e.g., a subject's blood), the method comprising ex vivo contacting the fluid (e.g., a subject's blood) with a device comprising a cell-derived membrane. In some embodiments, the method comprises ex vivo contacting the fluid (e.g., a subject's blood) with a device comprising a cartridge or adsorbent comprising a cell-derived membrane or an EBP device. In some embodiments, the method comprises ex vivo contacting the fluid (e.g., a subject's blood) with a device assembly comprising at least two of the above devices or EBP devices in fluid communication.

[0009] In some aspects, the present disclosure is related to U.S. Patent Application No. 13 / 827,906, filed March 14, 2013, published as US 2013 / 0337066 A1, International Application No. PCT / US2012 / 039411, filed May 24, 2012, published as WO 2013 / 052167 A2, and International Patent Application No. PCT / US2017 / 012342, filed February 5, 2017, published as WO 2017 / 120342 A1, the contents of which are incorporated by reference in their entirety.

[0010] V. Brief description of the drawings Those skilled in the art will understand that the drawings (described below) are for illustration purposes only and are not intended to limit the scope of the present teachings in any way.

[0011] The patent or application file contains at least one drawing produced in color. Copies of the patent or application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 illustrates the use of cell membranes as components for extracorporeal detoxification.

[0013] [Diagram 2] FIG. 2 illustrates examples of packaging cell membranes to create "membrane cartridges" for extracorporeal detoxification, including (A) cell membranes wrapped around nanofibers, (B) cell membranes spread on plates for detoxification, (C) cell membranes formed into vesicles or particles and embedded inside hydrogels for detoxification, and (D) cell membranes wrapped around magnetic particles for enrichment and isolation during the detoxification.

[0014] [Diagram 3] 3 illustrates an exemplary device assembly in which membrane cartridges are connected in series. Fluid (e.g., a subject's blood) can be passed through the membrane cartridges for continuous detoxification or substance removal. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] VI. DETAILED DESCRIPTION OF THE PRESENT EMBODIMENT The practice of the present invention will employ, unless otherwise indicated, conventional techniques of nanotechnology, nanoengineering, molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry, immunology, and pharmacology, which are within the skill of the art. Such techniques are fully explained in such references as: Molecular Cloning: A Laboratory Manual, 2nd Edition (Sambrook et al., 1989); Oligonucleotide Synthesis (MJ Gait, ed., 1984); Animal Cell Culture (RI Freshney, ed., 1987); Methods in Enzymology (Academic Press, Inc.); Current Protocols in Molecular Biology (FM Ausubel et al., ed., 1987, and periodic updates); PCR: The Polymerase Chain Reaction (Mullis et al., eds., 1994); Remington, The Science and Practice of Pharmacy, 20th Edition (Lippincott, Williams & Wilkins 2003), and Remington, The Science and Practice of Pharmacy, 22nd Edition (Pharmaceutical Press and Philadelphia College of Pharmacy at University of the Sciences 2012).

[0016] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs.All patents, applications, published applications and other publications mentioned herein are incorporated by reference in their entirety.If the definitions set forth in this section contradict or are otherwise inconsistent with the definitions set forth in the patents, applications, published applications and other publications incorporated by reference herein, the definitions set forth in this section shall prevail over the definitions incorporated by reference herein.

[0017] A.Definition To facilitate understanding of the present invention, a number of terms and abbreviations, as used herein, are defined below as follows.

[0018] When introducing elements of the invention or preferred embodiments thereof, the articles "a," "an," and "the" are intended to mean that one or more of the elements mentioned are present. The terms "comprising," "including," and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements.

[0019] The term "and / or," when used in a list of two or more items, means that any one of the listed items may be used alone or in combination with any one or more of the listed items. For example, the phrase "A and / or B" is intended to mean either or both of A and B (i.e., A alone, B alone, or a combination of A and B). The phrase "A, B and / or C" is intended to mean A alone, B alone, C alone, a combination of A and B, a combination of A and C, a combination of B and C, or a combination of A, B and C.

[0020] Cellular membrane: The term "cellular membrane" as used herein refers to a surrounding or separating structure of a biological membrane that acts as a selective barrier inside or around a cell or to emerging virus particles. The cellular membrane is selectively permeable to ions and organic molecules and controls the movement of materials into and out of the cell. The cellular membrane comprises a monolayer or bilayer of phospholipids, optionally associated with proteins and carbohydrates. As used herein, the cellular membrane refers to a membrane obtained from or derived from a naturally occurring biological membrane of a cell or cellular organelle. As used herein, the term "naturally occurring" refers to something that occurs in nature. As used herein, the term "derived therefrom" refers to any subsequent modification of the native membrane (e.g., isolating the cellular membrane, making a portion or fragment of the membrane, removing and / or adding certain components (lipids, proteins or carbohydrates) from or to a membrane taken from a cell or cellular organelle). Membranes can be obtained from naturally occurring membranes by any suitable method. For example, membranes can be prepared or isolated from cells, and the prepared or isolated membranes can be combined with other materials to form the resulting membrane. In another example, cells can be recombinantly engineered to produce "non-natural" materials that are incorporated into the membrane in vivo, and the cell membranes can be prepared or isolated from the cells to form the resulting membrane.

[0021] In various embodiments, the cell membrane covering either the unilamellar or multilamellar nanoparticles or nanostructures may be further modified to be saturated or unsaturated with other lipid components (e.g., cholesterol, free fatty acids, and phospholipids) and may also contain endogenous or added proteins and carbohydrates (e.g., cell surface antigens). In such cases, excess amounts of other lipid components may be added to the membrane wall where they are repelled until the concentration in the membrane wall reaches equilibrium. This may depend on the nanoparticle environment. The membrane may also contain other agents that may or may not increase the activity of the nanoparticle or nanostructure. In other examples, functional groups (e.g., antibodies and aptamers) may be added to the outer surface of the membrane to enhance site targeting (e.g., to cell surface epitopes found in cancer cells). The membrane of the nanoparticle or nanostructure may also contain particles that may be biodegradable, cationic nanoparticles (including but not limited to gold, silver, and synthetic nanoparticles).

[0022] Synthetic or artificial membrane: As used herein, the term "synthetic membrane" or "artificial membrane" refers to a man-made membrane made from organic (e.g., polymers and lipids) and inorganic materials. A wide variety of synthetic membranes are well known in the art.

[0023] Nanoparticles: In some embodiments, the term "nanoparticle" as used herein refers to nanostructures, particles, vesicles, or fragments thereof having at least one dimension (e.g., height, length, width, or diameter) between about 1 nm and about 10 μm. For systemic use, an average diameter of about 50 nm to about 500 nm, or 100 nm to 250 nm, may be preferred. The term "nanostructure" includes, but is not necessarily limited to, particles and engineered features. The particles and engineered features may have, for example, regular or irregular shapes. Such particles are also referred to as nanoparticles. The nanoparticles may be composed of organic or other materials, or may be implemented as porous particles. The layer of nanoparticles may be implemented with nanoparticles in a single layer, or with a layer having aggregations of nanoparticles. In some embodiments, the nanoparticles that comprise or consist of an internal compartment (or inner core) covered by an outer surface (or shell) include a membrane as discussed herein. The present disclosure includes any currently known and later developed nanoparticles that can be coated with the membranes described herein.

[0024] In certain embodiments, the term "nanostructure" as used herein refers to a structure (e.g., nanofiber, nanotube, nanowire, or nanosheet) having at least one dimension (e.g., height, length, width, and diameter) between about 1 nm and about 10 μm. A "nanostructure" can be a 1D nanostructure or a 2D nanostructure. The dimensional parameters of the second and / or third dimension may or may not be in a dimensional range (e.g., height, length, width, or diameter) between about 1 nm and about 10 μm. The term "nanostructure" includes, but is not limited to, nanofiber, nanotube, nanowire, or nanosheet, and engineered features. The nanostructures and engineered features can have, for example, regular or irregular shapes. The nanostructures can be composed of inorganic, organic, or other materials, or can be implemented in porous materials. The layer of nanostructures can be implemented with nanostructures in a single layer, or with agglomerations of nanostructures. In some embodiments, the nanostructure has an inner core covered by an outer surface comprising a cell-derived membrane. The present invention contemplates any now known and later developed nanostructure that can be coated with the membranes described herein.

[0025] Pharmaceutically active: The term "pharmacologically active" as used herein refers to the beneficial biological activity of a substance on a living organism, and in particular on the cells and tissues of the human body. A "pharmacologically active agent" or "drug" is a substance that is pharma- ceutical active, and a "pharmaceutical active ingredient" (API) is the pharma- ceutical active substance in a drug.

[0026] Pharmaceutically acceptable: The term "pharmaceutical acceptable," as used herein, means approved by a federal or state regulatory agency or listed in the United States Pharmacopeia or other generally recognized pharmacopoeias, in addition to other formulations that are safe for use in animals, and more particularly, in humans and / or non-human mammals.

[0027] Pharmaceutically acceptable salt: The term "pharmaceutical acceptable salt" as used herein refers to an acid or base addition salt of a compound (e.g., a multi-drug conjugate) in the present disclosure. A pharmaceutical acceptable salt is any salt that retains the activity of the parent nanoparticle or compound and does not impart any harmful or undesirable effects to the subject to which it is administered and in the context in which it is administered. Pharmaceutically acceptable salts may be derived from amino acids, including but not limited to cysteine. Methods for producing compounds as salts are known to those skilled in the art (see, for example, Stahl et al., Handbook of Pharmaceutical Salts: Properties, Selection, and Use, Wiley-VCH; Verlag Helvetica Chimica Acta, Zurich, 2002; Berge et al., J Pharm. Sci. 66: 1, 1977). In some embodiments, "pharmaceutical acceptable salt" is intended to mean a free acid or base salt of the nanoparticles or compounds described herein that is non-toxic, biologically acceptable, or otherwise biologically suitable for administration to a subject. See generally, Berge, et al., J. Pharm. Sci., 1977, 66, 1-19. Preferred pharmaceutical acceptable salts are those that are pharmacologically effective and suitable for contact with the tissues of a subject without undue toxicity, irritation, or allergic response. The nanoparticles or compounds described herein may have sufficiently acidic groups, sufficiently basic groups, both types of functional groups, or more than one of each type, and react with many inorganic or organic bases, as well as inorganic and organic acids, to form pharmaceutical acceptable salts.

[0028] Examples of pharma- ceutically acceptable salts include sulfates, pyrosulfates, hydrogen sulfates, sulfites, bisulfites, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne-1,4-dioate, hexyne-1,6-dioate, benzoates, and the like. These include benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, sulfonate, methylsulfonate, propylsulfonate, besylate, xylenesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, [gamma]-hydroxybutyrate, glycolate, tartrate, and mandelate salts.

[0029] Pharmaceutically acceptable carrier: The term "pharmaceutical acceptable carrier" as used herein refers to an excipient, diluent, preservative, solubilizer, emulsifier, adjuvant, and / or vehicle with which nanoparticles or compounds (e.g., multi-drug conjugates) are administered together. Such carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin (e.g., peanut oil, soybean oil, mineral oil, sesame oil, etc., polyethylene glycol, glycerin, propylene glycol, or other synthetic solvents). Antibacterial agents (e.g., benzyl alcohol or methyl parabens); antioxidants (e.g., ascorbic acid or sodium bisulfite); chelating agents (e.g., ethylenediaminetetraacetic acid); and agents for adjusting tonicity (e.g., sodium chloride or dextrose) can also be carriers. Methods for combining with carriers to produce compositions are known to those skilled in the art. In some embodiments, the phrase "pharmaceutically acceptable carrier" is intended to include any and all solvents, dispersion media, coatings, isotonic and absorption retarding agents, etc., that are compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is well known in the art. For example, see Remington, The Science and Practice of Pharmacy. 20th Edition, (Lippincott, Williams & Wilkins 2003). Except insofar as any conventional media or agent is incompatible with the active compound, its use in the above composition is contemplated.

[0030] Phospholipid: The term "phospholipid" as used herein refers to any of a number of lipids that contain glyceride, phosphate group, and simple organic molecules (e.g., choline). Examples of phospholipids include, but are not limited to: phosphatidic acid (phosphatidate) (PA), phosphatidylethanolamine (cephalin) (PE), phosphatidylcholine (lecithin) (PC), phosphatidylserine (PS), and phosphoinositides (including, but not limited to, phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), phosphatidylinositol bisphosphate (PIP2) and phosphatidylinositol triphosphate (P1P3)). Further examples of PC include DDPC, DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DRPC, and DEPC (as defined in the art).

[0031] Therapeutically effective amount: As used herein, the term "therapeutically effective amount" refers to those amounts that, when administered to a particular patient or contacted ex vivo with a subject's fluid (e.g., the subject's blood), have the desired therapeutic effect, taking into account the nature and severity of the subject's disease or condition, e.g., the amount that cures, prevents, inhibits, or at least partially stops or partially prevents the target disease or condition. In some embodiments, the term "therapeutically effective amount" or "effective amount" refers to the amount of a therapeutic agent that, when administered alone or in combination with an additional therapeutic agent to a cell, tissue, or subject, is effective to prevent or ameliorate the disease or condition (e.g., a hemolytic disease or condition) or the progression of the disease or condition. A therapeutically effective dose further refers to that amount of a therapeutic agent that is sufficient to cause an improvement in symptoms (e.g., treatment, cure, prevention, or amelioration of an associated medical condition) or to increase the rate of treatment, cure, prevention, or amelioration of such a condition. When applied to an individual active ingredient administered alone, a therapeutically effective dose refers to that ingredient alone When applied to a combination, a therapeutically effective dose refers to the combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, serially, or simultaneously.

[0032] "Treating" or "treatment" or "alleviation" refers to a therapeutic treatment that does not cure the subject or slow (reduce) if not prevent the recurrence of the targeted pathological condition or disorder. A subject is successfully "treated" if, after receiving a therapeutic amount of a therapeutic agent, the subject shows an observable and / or measurable reduction or absence of one or more signs and symptoms of the particular disease. The reduction of the signs or symptoms of the disease can also be felt by the patient. A patient is also considered to be treated if the patient experiences symptom stabilization. In some embodiments, treatment with a therapeutic agent is effective to cause the patient to be disease-free for 3 months, preferably 6 months, more preferably 1 year, even more preferably 2 years or more years after treatment. These parameters for evaluating successful treatment and improvement in the disease are easily measurable by routine procedures familiar to a physician of appropriate skill in the art.

[0033] As used herein, "preventative" treatment is meant to indicate postponing the onset of a disease, symptom of a disease, or medical condition, inhibiting symptoms that may appear, or reducing the risk of the onset or recurrence of a disease or condition. "Curative" treatment includes reducing the severity or inhibiting the progression of an existing disease, symptom, or condition.

[0034] The term "combination" refers to either a fixed combination in one dosage unit form or a kit of parts, where the nanoparticles or compound and the combination partner (e.g., another drug as described below (also referred to as a "therapeutic agent" or "co-agent")) can be administered separately at the same time or within a time interval, particularly for combined administration when these time intervals allow the combination partners to exhibit a coordinated (e.g., synergistic) effect. The terms "co-administration" or "combined administration" and the like, as used herein, are meant to encompass the administration of selected combination partners to a single subject (e.g., patient) in need thereof, and are intended to include treatment regimens in which the agents are not necessarily administered by the same route of administration or at the same time. The term "pharmaceutical combination" as used herein refers to a product resulting from the mixing or combination of more than one active ingredient, including both fixed and non-fixed combinations of the active ingredients. The term "fixed combination" means that the active ingredients (e.g., nanoparticles or compounds and combination partners) are both administered to a patient simultaneously in the form of a single entity or dosage. The term "non-fixed combination" means that the active ingredients (e.g., nanoparticles or compounds and combination partners) are both administered to a patient as separate entities, either simultaneously, concurrently or sequentially, without any specific time limit, where such administration provides therapeutically effective levels of the two moieties or compounds in the patient's body. The latter also applies to cocktail therapy (e.g., administration of three or more active ingredients).

[0035] It is understood that aspects and embodiments of the invention described herein include aspects and embodiments of "consisting of" and / or "consisting essentially of".

[0036] Throughout this disclosure, various aspects of the invention are presented in range format. It should be understood that the descriptions in range format are for convenience and brevity only and should not be construed as an inflexible limitation on the scope of the invention. Thus, a description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as the individual numerical values within that range. For example, a range description such as 1 to 6 should be considered to have specifically disclosed sub-ranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as the individual numbers within that range (e.g., 1, 2, 3, 4, 5, and 6). This applies regardless of the width of the range.

[0037] As used herein, a subject in need refers to an animal, non-human mammal or human. As used herein, "animal" includes pets, livestock, economic animals, sport animals and laboratory animals (cats, dogs, horses, cows, oxen, pigs, donkeys, sheep, lambs, goats, mice, rabbits, chickens, ducks, geese, primates (including monkeys and chimpanzees)).

[0038] Other objects, advantages and features of the present invention will become apparent from the following description when understood in conjunction with the accompanying drawings.

[0039] B. Membrane-containing cartridge or sorbent-containing device In one aspect, the present disclosure provides a device (e.g., an extracorporeal blood purification (EBP) device) comprising a cartridge or adsorbent comprising a cell membrane derived from a cell.

[0040] In the devices of the present invention, the cartridge or adsorbent may have any suitable ratio between the surface area of ​​the cell membrane and the volume of the cartridge or adsorbent. In some embodiments, the cartridge or adsorbent has a ratio of about 1 m between the surface area of ​​the cell membrane and the volume of the cartridge or adsorbent. -1 ~Approx. 3×10 8 m -1 For example, about 1 m -1 , 10m -1 , 100m -1 , 1,000m -1 , 1×10 4 m -1 , 1×10 5 m -1 , 1×10 6 m -1 , 1×10 7 m -1 , 1×10 8 m -1 , 3×10 8 m -1 or any subrange thereof.

[0041] In the device of the present invention, the cartridge or adsorbent may comprise a cell membrane derived from a cell in any suitable form. For example, in the device of the present invention, the cartridge or adsorbent may comprise nanoparticles comprising the cell membrane, nanostructures (e.g., nanofibers) comprising the cell membrane, plenary surfaces comprising the cell membrane, or combinations thereof.

[0042] In some embodiments, in the device of the present invention, the cartridge or adsorbent comprises nanoparticles that comprise the cell membrane. Any suitable nanoparticles can be used in the device of the present invention. For example, in the device of the present invention, the cartridge or adsorbent can comprise nanoparticles that comprise a) an inner core that comprises non-cellular material; and b) an outer surface that comprises cell membrane derived from cells. Other suitable or exemplary nanoparticles described and / or claimed in US 2013 / 337066 A1 and WO 2013 / 052167 A2 can also be used.

[0043] In some embodiments, in the device of the present invention, the cartridge or adsorbent comprises a nanostructure (e.g., nanofiber) comprising the cell membrane. Any suitable nanostructure or nanofiber can be used in the device of the present invention. For example, in the device of the present invention, the cartridge or adsorbent can comprise a nanostructure comprising: a) an inner core comprising non-cellular material; and b) an outer surface comprising a cell membrane derived from a cell, wherein the nanostructure has: 1) a first dimension having a first dimensional parameter ranging from about 1 nm to about 10 μm and a second dimension having a second dimensional parameter of at least about 11 nm; and / or 2) a first dimension having a first dimensional parameter ranging from about 1 nm to about 10 μm and a second dimension having a second dimensional parameter, the second dimension having a ratio between the second dimensional parameter and the first dimensional parameter of at least about 2. WO 2017 / 120342 A1 and Wansong Chen et al., "Coating nanofiber scaffolds with beta cell membrane to promote cell proliferation and function", Nanoscale, 8 Other suitable or exemplary nanostructures or nanofibers described and / or claimed in US Pat. No. 6,364,413 (2016) may also be used.

[0044] In some embodiments, in the device of the present invention, the cartridge or adsorbent includes the entire surface including the cell membrane. The cell membrane can be arranged on the entire surface in any suitable manner. For example, the cell membrane can be coated or spread on the entire surface. In another example, the cell membrane is a cellular membrane as described in Hua Gong et al., "Biomembrane-Modified Field Effect Transistors for Sensitive and Quantitative Detection of Biological Toxins and Pathogens", ACS Nano, 13:3714-3722 (2019) may be disposed on all of the above surfaces.

[0045] In some embodiments, in the device of the present invention, the cartridge or adsorbent comprises at least two of the following: 1) nanoparticles comprising the cell membrane; 2) nanostructures (e.g., nanofibers) comprising the cell membrane; and 3) the entire surface comprising the cell membrane. For example, in the device of the present invention, the cartridge or adsorbent may comprise nanoparticles comprising the cell membrane and nanostructures (e.g., nanofibers) comprising the cell membrane; nanoparticles comprising the cell membrane and the entire surface comprising the cell membrane; or nanostructures (e.g., nanofibers) comprising the cell membrane and the entire surface comprising the cell membrane. In some embodiments, in the device of the present invention, the cartridge or adsorbent comprises 1) nanoparticles comprising the cell membrane; 2) nanostructures (e.g., nanofibers) comprising the cell membrane; and 3) the entire surface comprising the cell membrane.

[0046] In the device of the present invention, the cartridge or adsorbent may include any suitable cell membrane. In some embodiments, in the device of the present invention, the cartridge or adsorbent may include a plasma membrane or a unilamellar (e.g., bacteria or fungi) or an intracellular membrane derived from a multicellular organism (e.g., a plant, an animal, a non-human mammal, a vertebrate, or). In some embodiments, in the device of the present invention, the cartridge or adsorbent may include a naturally occurring cell membrane, a modified cell membrane, or a combination or fusion of a naturally occurring cell membrane and a modified cell membrane. For example, in the device of the present invention, the cartridge or adsorbent may include a combination or fusion of a naturally occurring cell membrane and a modified cell membrane, or a combination or fusion of a naturally occurring cell membrane and a synthetic membrane. In another example, in the device of the present invention, the cartridge or adsorbent may include a combination or fusion of a naturally occurring cell membrane, a modified cell membrane, and a synthetic membrane.

[0047] The cell membrane can be modified in any suitable manner.For example, in the device of the present invention, the cartridge or adsorbent can contain cell membranes with altered or enhanced levels of hormones such as cholesterol and / or altered or enhanced levels of lipids such as sphingomyelin (see, for example, US 2015 / 0157570 A1).In some embodiments, in the device of the present invention, the cartridge or adsorbent can contain cell membranes with altered or enhanced levels of cholesterol and sphingomyelin.

[0048] In various embodiments, the cell membrane in the device of the present invention may be further modified to be saturated or unsaturated with other lipid components (e.g., cholesterol, free fatty acids, and phospholipids) and may also contain endogenous or added proteins and carbohydrates (e.g., cell surface antigens). In such cases, excess amounts of other lipid components may be added to the membrane wall where they are repelled until their concentration in the membrane wall reaches equilibrium. This may depend on the environment of the nanoparticle or nanostructure. The membrane may also contain other agents that may or may not increase the activity of the device of the present invention. In other examples, functional groups (e.g., antibodies and aptamers) may be added to the outer surface of the membrane to enhance site targeting (e.g., to cell surface epitopes). The cell membrane of the device of the present invention may also contain particles that may be biodegradable, cationic nanoparticles (including but not limited to gold, silver, and synthetic nanoparticles) (see, e.g., WO 2017 / 120342 A1).

[0049] In some embodiments, in the device of the present invention, the cartridge or adsorbent includes cell membranes derived from blood cells, tumor cells, cancer cells, immune cells, stem cells, endothelial cells, nerve cells, exosomes, secretory vesicles, and / or synaptic vesicles. In some embodiments, in the device of the present invention, the cartridge or adsorbent includes cell membranes derived from red blood cells, platelets, macrophages, neutrophils, and / or nerve cells. In some embodiments, in the device of the present invention, the cartridge or adsorbent includes cell membranes derived from macrophages. In some embodiments, in the device of the present invention, the cartridge or adsorbent includes cell membranes derived from macrophages and neutrophils. In some embodiments, in the device of the present invention, the cartridge or adsorbent includes cell membranes derived from red blood cells and platelets. In some embodiments, in the device of the present invention, the cartridge or adsorbent includes cell membranes derived from red blood cells, platelets, and nerve cells.

[0050] The device of the present invention can have any suitable dimensions (e.g., suitable length and cross-sectional surface area). In some embodiments, the device of the present invention can have a length ranging from 0.01 m to 1 m (meter) (e.g., about 0.01 m, 0.02 m, 0.03 m, 0.04 m, 0.05 m, 0.06 m, 0.07 m, 0.08 m, 0.09 m, 0.1 m, 0.2 m, 0.3 m, 0.4 m, 0.5 m, 0.6 m, 0.7 m, 0.8 m, 0.9 m, 1 m, or any partial range thereof). In some embodiments, the device of the present invention is 2.5×1 0 -5 m 2 (square meter) to about 0.01 m 2 (square meter) (e.g., about 2.5×1 0 -5 m 2 、5×1 0 -5 m 2 、1×1 0 -4 m 2 、1×1 0 -3 m 2 、.01 m2 、 or have a cross-sectional surface area extending over (or any partial range thereof).

[0051] The device of the present invention can have any suitable shape. For example, the device of the present invention can be configured as a column, where the cartridge or adsorbent is positioned or packed inside a tube. In another example, the device of the present invention can be configured as a flat device, where the cartridge or adsorbent is present as a surface or on a surface.

[0052] The device of the present invention can be configured for any suitable use or purpose. For example, the device of the present invention can be configured as an extracorporeal blood purification (EBP) device.

[0053] In the device of the present invention, the cartridge or adsorbent can include the cell membranes derived from any suitable cell type or number. In some embodiments, in the device of the present invention, the cartridge or adsorbent includes the cell membranes derived from a single cell type. In some embodiments, in the device of the present invention, the cartridge or adsorbent includes the cell membranes derived from different cell types.

[0054] In another aspect, the present disclosure provides a device assembly including at least two of the above devices, where the at least two devices are in fluid communication and include cartridges or adsorbents containing cell membranes derived from different cell types. For example, the device assembly of the present invention can include 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50 or more of the above devices in tandem (or continuous) fluid communication.

[0055] C. Methods for Removing or Reducing Substances from a Liquid In yet another aspect, the present disclosure provides a method for removing or reducing a substance from a fluid (e.g., a fluid obtained from a subject), the method comprising contacting the fluid (e.g., a fluid obtained from a subject) ex vivo with a device comprising a cell membrane derived from a cell.

[0056] The methods of the present invention can be used to remove or reduce substances from any suitable liquid (e.g., any suitable liquid obtained from a subject). For example, the methods of the present invention can be used to remove or reduce substances (e.g., unwanted substances) from blood or urine from a subject. In some embodiments, the present disclosure provides a method for removing or reducing substances (e.g., unwanted substances) from a subject's blood, comprising ex vivo contacting the subject's blood with a device comprising a cell membrane derived from a cell.

[0057] Any suitable device or device assembly can be used in the methods of the invention. In some embodiments, the methods of the invention include contacting a liquid (e.g., liquid obtained from a subject, blood, urine) with the device or device assembly.

[0058] The methods of the invention may be used to remove or reduce any suitable unwanted material from a fluid (e.g., any suitable fluid, blood or urine obtained from a subject). For example, the methods of the invention may be used to remove or reduce waste products, cytokines (e.g., pro-inflammatory cytokines), and / or toxins in a fluid (e.g., any suitable fluid, blood or urine obtained from a subject). The methods of the invention may be used to remove or reduce any suitable toxin type (e.g., a viral, bacterial, fungal, plant and / or animal toxin).

[0059] The method of the present invention can be used to remove or reduce any suitable unwanted material from the fluid of any suitable subject. For example, the subject is a mammal. In some embodiments, the mammal is a non-human mammal. In some embodiments, the mammal is a human (e.g., a human patient).

[0060] The method of the present invention can be used to remove or reduce unwanted substances from a liquid to an appropriate or desired extent. For example, the method of the present invention can be used to substantially remove or reduce all substances from a liquid or blood of a subject that target or attack target cells of the subject. In some embodiments, the method of the present invention can be used to substantially remove at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or more of the substances from a liquid or blood of a subject that target or attack target cells of the subject. In another example, the method of the present invention can be used to substantially remove or reduce all pathological or pathogenic agents from a liquid or blood of a subject that target or attack target cells of the subject. In some embodiments, the methods of the present invention may be used to substantially remove from a fluid or fluid of a subject at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or more of pathological or pathogenic agents that target or attack target cells of said subject.

[0061] In some embodiments, the subject's target cell and the cell from which the cell membrane is derived are the same cell type. In some embodiments, the subject's target cell and the cell from which the cell membrane is derived are different cell types.

[0062] The method of the present invention can be used for any suitable use or purpose. In some embodiments, the method of the present invention is used for hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF) or high flux dialysis (HFD). In some embodiments, the method of the present invention is used to treat or prevent renal failure, liver failure or sepsis in a subject. In some embodiments, the method of the present invention is used to treat or prevent infection, severe infection and / or sepsis in a subject, where the cell membrane is derived from a macrophage. In some embodiments, the method of the present invention is used to treat or prevent inflammatory disorders or severe inflammatory disorders (e.g., rheumatoid arthritis or pancreatitis) in a subject, where the cell membrane is derived from a macrophage and / or a neutrophil. In some embodiments, the method of the present invention is used to treat or prevent autoimmune diseases (e.g., autoimmune anemia) in a subject, where the cell membrane is derived from a red blood cell and / or a platelet. In some embodiments, the methods of the invention are used to treat or prevent a chemical or biological weapon attack in a subject, where the cell membrane is derived from a red blood cell, platelet, and / or neuron. In some embodiments, the methods of the invention are used to treat or prevent an animal envenomation (e.g., a lethal animal envenomation) in a subject, where the cell membrane is derived from a red blood cell, platelet, and / or neuron.

[0063] The method of the present invention can use any suitable number of devices or device assemblies. In some embodiments, the method of the present invention uses a single device or device assembly. In some embodiments, the method of the present invention uses a number of devices or device assemblies. In some embodiments, the method of the present invention uses a number of devices or device assemblies to remove or reduce a number of substances from a liquid (e.g., a subject's liquid or blood). In some cases, each of the devices in the above-mentioned number of devices or device assemblies is used to remove or reduce a specific (or specific type of) substance from a liquid (e.g., a subject's liquid or blood).

[0064] D. Exemplary Embodiments In some embodiments, the present invention selectively captures and removes substantially all or all pathogenic or pathogenic factors that attack cells in another way with respect to biological activity using a membrane derived from living cells as an active component (Figure 1). Compared with existing technologies, membrane-based detoxification has unique advantages. (1) By selecting membranes derived from different cell types, the device can be used for different diseases. (2) The cell membrane exhibits an accurate antigen profile as the source cell. Therefore, the device can remove toxins without the need to identify individual toxin components. (3) By acting as an agent for target cells, these devices can capture toxins by accurately mapping the complexity and diversity of disease pathology. (4) Since the cell membranes are derived from different cell types, a similar manufacturing process is followed, which facilitates or ensures the scalability of the technology.

[0065] In some embodiments, cell membranes are combined with other engineering approaches such as nanotechnology to pack into a filter / cartridge to create a membrane cartridge (Figure 2). By combining with nanotechnology, the surface-to-volume ratio of the material is significantly increased. This allows a large amount of membranes to be packed into a small volume for detoxification. For example, membranes can be formulated into nanoparticles. In some cases, the nanoparticles can be either embedded into hydrogels for retention or wrapped around magnetic particles for enrichment and isolation. Membranes can also be spread over the entire surface or onto fibers that allow fluid to pass through and the toxins to be captured.

[0066] In some embodiments, for treatment, specific cell types can be selected to obtain membranes and applied to treat different diseases (see, for example, Table 1). For example, to treat severe infections and sepsis, membranes derived from macrophages can be used. To treat severe inflammatory disorders (e.g., rheumatoid arthritis or pancreatitis), membranes derived from neutrophils can be used. To treat serious autoimmune diseases (e.g., autoimmune anemia), membranes derived from red blood cells (RBCs) can be used. To treat chemical and biological weapon attacks or lethal animal envenomations, membranes derived from RBCs or nerve cells can be used. [Table 1]

[0067] In some embodiments, given the complexity of the disease, membranes from multiple cells may be used, in which case membrane cartridges may be connected in series and the fluid may undergo continuous detoxification (Figure 3). In certain embodiments, for example, the following are provided: (Item 1) A device comprising a cartridge or adsorbent containing cell-derived membranes, such as an extracorporeal blood purification (EBP) device. (Item 2) The cartridge or sorbent is about 1 m-1 ~Approx. 3×10 8 m -1 2. The device of claim 1, having a ratio between the surface area of ​​the cell membrane and the volume of the cartridge or sorbent ranging from 0.1 to 1. (Item 3) 3. The device of claim 1 or 2, wherein the cartridge or sorbent comprises a nanoparticle comprising the cell membrane, a nanostructure (e.g., a nanofiber) comprising the cell membrane, an entire surface comprising the cell membrane, or a combination thereof. (Item 4) 4. The device according to any one of items 1 to 3, wherein the cartridge or adsorbent comprises nanoparticles comprising the cell membrane. (Item 5) The nanoparticles are a) an inner core that contains non-cellular material; and b) an outer surface comprising a plasma membrane derived from a cell; 5. The device according to item 4, comprising: (Item 6) 6. The device of claim 5, wherein the inner core of the nanoparticle supports the outer surface of the nanoparticle. (Item 7) 7. The device of item 5 or 6, wherein the inner core comprises a biocompatible material or a synthetic material selected from the group consisting of poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polylysine, and polyglutamic acid. (Item 8) 8. The device according to any one of items 3 to 7, wherein the cell membrane of the nanoparticle comprises a plasma membrane or an intracellular membrane. (Item 9) 9. The device according to any one of items 3 to 8, wherein the cell membrane of the nanoparticles is derived from a multicellular organism (e.g., a plant, a vertebrate, an animal, a non-human mammal or a human). (Item 10) 10. The device of any one of items 3 to 9, wherein the nanoparticles further comprise a releasable cargo. (Item 11) 11. The device of claim 10, wherein the releasable cargo is located within or on the inner core, between the inner core and the outer surface, or within or on the outer surface. (Item 12) 12. The device according to item 10 or 11, wherein release of the releasable cargo is triggered by contact between the nanoparticles and a liquid, such as the blood of a subject. (Item 13) 13. The device according to any one of items 10 to 12, wherein the releasable cargo is a therapeutic agent, a preventative agent, a diagnostic or marker agent, a prognostic agent, an isolation agent, or a combination thereof. (Item 14) 14. The device according to any one of items 1 to 13, wherein the releasable cargo is a metal particle, a polymer particle, a dendrimer particle, or an inorganic particle. (Item 15) 15. The device according to any one of items 3 to 14, wherein the nanoparticles have a diameter of about 10 nm to about 10 μm. (Item 16) 16. The device of any one of items 3 to 15, wherein the nanoparticles are substantially devoid of components of the cell from which the cell membrane is derived. (Item 17) 17. The device of any one of items 3 to 16, wherein the cell membrane of the nanoparticles comprises a plasma membrane derived from a red blood cell, and the nanoparticles are substantially devoid of hemoglobin. (Item 18) 17. The device of any one of items 3 to 16, wherein the nanoparticles substantially maintain the native structural integrity or activity of the cell membrane, or components of the cell membrane. (Item 19) 19. The device according to any one of items 3 to 18, wherein the nanoparticles are biocompatible or biodegradable. (Item 20) 20. The device of any one of items 3 to 19, wherein the inner core of the nanoparticle comprises PLGA and the outer surface comprises a plasma membrane derived from a red blood cell. (Item 21) 21. The device of claim 20, wherein the inner core of the nanoparticle comprises PLGA and the outer surface comprises a plasma membrane derived from a human red blood cell. (Item 22) 22. The device of any one of items 3 to 21, wherein the nanoparticles are substantially devoid of immunogenicity for the species or subject from which the cell membrane is derived. (Item 23) 23. The device of any one of items 3 to 22, wherein the outer surface comprises a naturally occurring cell membrane and further comprises a modified cell membrane and / or a synthetic membrane. (Item 24) The device according to any one of items 1 to 3, wherein the cartridge or adsorbent comprises a nanostructure (e.g., a nanofiber) comprising the cell membrane. (Item 25) The nanostructure comprises: a) an inner core comprising non-cellular material; and b) an outer surface comprising a plasma membrane derived from a cell; wherein the nanostructure comprises: 1) having a first dimension having a first dimensional parameter ranging from about 1 nm to about 10 μm and a second dimension having a second dimensional parameter of at least about 11 nm; and / or 2) having a first dimension having a first dimensional parameter ranging from about 1 nm to about 10 μm, a second dimension having a second dimensional parameter, and a ratio between the second dimensional parameter and the first dimensional parameter of at least about 2; Item 25. The device according to item 24. (Item 26) 26. The device of claim 25, wherein the inner core of the nanostructure comprises an inorganic material, an organic material, or an aggregate or composite thereof. (Item 27) The inorganic material in the inner core of the nanostructure can be a superconducting material (e.g., YBCO), a metallic material (e.g., Ni, Pt, or Au), a semiconductor material (e.g., Si, InP, or GaN), an insulating material (e.g., SO 2 or T1O 2 27. The device of claim 26, comprising a metal-containing ligand, an ion (e.g., a sodium, potassium, magnesium, calcium, chloride, iron, copper, zinc, manganese, cobalt, iodine, molybdenum, vanadium, nickel, chromium, fluorine, silicon, tin, boron or arsenic ion), or a coordination complex (e.g., a metal-containing coordination complex). (Item 28) 27. The device of claim 26, wherein the organic material in the inner core of the nanostructure is selected from the group consisting of amino acids, peptides, proteins, nucleosides, nucleotides, oligonucleotides, nucleic acids such as DNA or RNA, vitamins, monosaccharides, oligosaccharides, carbohydrates, lipids, or aggregates or complexes thereof. (Item 29) 29. The device of any one of items 24 to 28, wherein the non-cellular material of the inner core of the nanostructure comprises a polymer. (Item 30) 30. The device of item 29, wherein the polymer is selected from the group consisting of poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polylysine, polyglutamic acid and hydrophobic polymers that coil when switched from an organic solvent to an aqueous phase (e.g., water). (Item 31) 31. The device of any one of items 24 to 30, wherein the nanostructured inner core comprises a biocompatible material and / or a synthetic material. (Item 32) 32. The device of any one of claims 24 to 31, wherein an inner core of the nanostructure supports an outer surface of the nanostructure. (Item 33) 33. The device according to any one of items 24 to 32, wherein the cell membrane comprises a plasma membrane or an intracellular membrane. (Item 34) 34. The device according to any one of items 24 to 33, wherein the cell membrane is derived from a multicellular organism. (Item 35) 35. The device of item 34, wherein the multicellular organism is an animal, a plant or a filamentous fungus. (Item 36) Item 36. The device of item 35, wherein the animal is an invertebrate or a vertebrate. (Item 37) Item 37. The device of item 36, wherein the vertebrate is a fish, amphibian, reptile, bird or mammal. (Item 38) 38. The device of item 37, wherein the mammal is a non-human mammal. (Item 39) 39. The device of item 38, wherein the non-human mammal is a Rodent (e.g., mouse, rat, porcupine, beaver, or capybara), Chiroptera (e.g., bat), Soricomorpha (e.g., shrew, mole, or solenodon), Primate (e.g., Prosimian (e.g., Madagascar lemur, loris, or tarsier), or Ape (e.g., monkey, ape, or orangutan), Cetacea (e.g., whale) or Artiodactyla, or Carnivora (e.g., cat, dog, weasel, bear, or seal). (Item 40) Item 39. The device of item 38, wherein the mammal is a human. (Item 41) 41. The device of any one of items 24 to 40, wherein the nanostructure further comprises a releasable cargo. (Item 42) 42. The device of claim 41, wherein the releasable cargo is located within or on the inner core, between the inner core and the outer surface, or within or on the outer surface. (Item 43) 43. The device of item 41 or 42, wherein release of the releasable cargo is triggered by contact between the nanoparticles and a liquid (e.g., the blood of a subject). (Item 44) 45. The device of any one of items 24 to 44, wherein the releasable cargo is a therapeutic agent, a preventative agent, a diagnostic or marker agent, a prognostic agent, an isolation agent, or a combination thereof. (Item 45) 45. The device according to any one of items 41 to 44, wherein the releasable cargo is a metal particle, a polymer particle, a dendrimer particle, or an inorganic particle. (Item 46) 46. ​​The device of any one of items 24 to 45, wherein the nanostructure is substantially devoid of components of the cell from which the cell membrane is derived. (Item 47) 47. The device of any one of items 24 to 46, wherein the cell membrane of the nanostructure comprises a plasma membrane derived from a red blood cell, and the nanostructure is substantially devoid of hemoglobin. (Item 48) 48. The device of any one of items 24 to 47, wherein the nanostructure substantially maintains the native structural integrity or activity of the cell membrane, or components of the cell membrane. (Item 49) 49. The device of any one of items 24 to 48, wherein the nanostructure is biocompatible or biodegradable. (Item 50) 50. The device of any one of items 24 to 49, wherein the inner core of the nanostructure comprises PLGA and the outer surface comprises a plasma membrane derived from a red blood cell. (Item 51) 41. The device of any one of items 24 to 40, wherein the nanostructure is substantially devoid of immunogenicity to the species or subject from which the cell membrane is derived. (Item 52) 52. The device of any one of items 24 to 51, wherein the outer surface of the nanostructure comprises a naturally occurring cell membrane and further comprises a modified cell membrane and / or a synthetic membrane. (Item 53) 53. The device of claim 52, wherein the naturally occurring cell membrane, the modified cell membrane and / or the synthetic membrane comprises a modification. (Item 54) 54. The device of item 53, wherein the modification is a physical modification, a chemical modification, or a biological modification, for example, a modification via genetic manipulation. (Item 55) 55. The device of any one of items 24 to 54, wherein the second dimensional parameter is at least about 11 nm and a ratio between the second dimensional parameter and the first dimensional parameter is at least about 10. (Item 56) 56. The device of any one of items 24 to 55, wherein the second dimensional parameter is at least about 1 mm. (Item 57) 57. The device of any one of items 24 to 56, wherein the ratio between the second dimensional parameter and the first dimensional parameter is at least about 1,000. (Item 58) 58. The device of claim 56 or 57, wherein the second dimensional parameter is at least about 1 mm and the ratio between the second dimensional parameter and the first dimensional parameter is at least about 1,000. (Item 59) 59. The device of any one of items 24 to 58, wherein the nanostructure is configured as a 1D nanostructure. (Item 60) Item 60. The device of item 59 configured as a nanofiber, nanotube or nanowire. (Item 61) Item 61. The device of item 60, wherein the second dimensional parameter (e.g., length) of the nanofiber, nanotube, or nanowire is at least about 1 cm, 1 m, or 10 m. (Item 62) 62. The device of any one of items 59 to 61, wherein the first dimension has a shape that includes a straight line segment, a shape that includes a polygon with a particular number of sides, a shape that includes a circular arc, or a shape that does not include a circular arc. (Item 63) Item 63. The device of item 62, wherein the shape comprising the straight line segments is selected from the group consisting of balbis, concave polygons, constructible polygons, convex polygons, cyclic polygons, equiangular polygons, equilateral polygons, Penrose tiles, polyforms, regular polygons, simple polygons and tangential polygons. (Item 64) Item 63. The device according to item 62, wherein the shape including a polygon having the specified number of sides is selected from the group consisting of a unilateral, a dilateral, a trilateral, a quadrilateral, a pentagon, a hexagon, a heptagon, an octagon, a nonagon, a decagon, an eleventh lateral, a dodecagon, a hexagon, a hexagon, a icosagon, and a star polygon. (Item 65) Item 63. The device according to item 62, wherein the shape comprising a circular arc is selected from the group consisting of an annulus, an arbelos, a circle (e.g., Archimedes' twin circle, Bankoff circle, circumscribing circle, disk, interscribing circle, inscribing circle, or nine-point circle), a sector, a circular segment, a crescent, an Indalo, a lens, a lune, a Reuleaux polygon, e.g., a Reuleaux triangle, a salinon, a semicircle, a tomahawk, and a triquetra. (Item 66) Item 63. The device of item 62, wherein the shape not including a circular arc is selected from the group consisting of Archimedes' spiral, an assteroid, a cardioid, a deltoid, an ellipse, a heart shape (geometric shape), a heart-shaped polygon, a lemniscate, an oval, e.g., a Cartesian oval, a Cassini oval or an Oval of Booth, an ovoid (shape), a super ellipse, a taijitu and a tomoe. (Item 67) 62. The device of any one of items 59 to 61, wherein the first dimension of the nanostructure has a shape selected from the group consisting of a sphere, a square, a rectangle, a triangle, a circular disk, and other regular or irregular shapes. (Item 68) 68. The device of any one of items 59 to 67, wherein the nanostructure further comprises a third dimension having a third dimensional parameter of at least about 11 nm and / or a ratio between the third dimensional parameter and the first dimensional parameter of at least about 10. (Item 69) Item 70. The device of item 68, wherein the third dimensional parameter is at least about 1 mm. (Item 70) Item 59. The device of item 58, wherein the ratio between the third dimensional parameter and the first dimensional parameter is at least about 1,000. (Item 71) 71. The device of claim 69 or 70, wherein the third dimensional parameter is at least about 1 mm and the ratio between the third dimensional parameter and the first dimensional parameter is at least about 1,000. (Item 72) 72. The device of any one of items 68 to 71, wherein the second dimensional parameter is at least about 1 mm. (Item 73) 72. The device of any one of items 68 to 71, wherein the ratio between the second dimensional parameter and the first dimensional parameter is at least about 1,000. (Item 74) 74. The device of claim 72 or 73, wherein the second dimensional parameter is at least about 1 mm and the ratio between the second dimensional parameter and the first dimensional parameter is at least about 1,000. (Item 75) 75. The device of any one of claims 68 to 74, wherein the nanostructure is configured as a 2D nanostructure. (Item 76) The nanostructure is the device according to item 75, configured as a nanosheet. (Item 77) The device according to item 76, wherein the second dimensional parameter (e.g., length) of the nanosheet is at least about 1 mm, 1 cm, 1 m or 10 m. (Item 78) The device according to item 76, wherein the third dimensional parameter (e.g., length) of the nanosheet is at least about 1 mm, 1 cm, 1 m or 10 m. (Item 79) The device according to item 77 or 78, wherein the second dimensional parameter (e.g., length) of the nanosheet and the third dimensional parameter (e.g., length) of the nanosheet are at least about 1 cm, 1 m or 10 m. (Item 80) The device according to any one of items 75 to 79, wherein the inner core of the 2D nanostructure contains carbon atoms (e.g., graphene) or metal atoms (e.g., palladium, rhodium, or gold atoms). (Item 81) The device according to any one of items 24 to 80, wherein the inner core of the nanostructure is prepared by a top-down process or a bottom-up process. (Item 82) The device according to any one of items 24 to 81, wherein the inner core of the nanostructure is prepared by a process selected from the group consisting of lithography, electrophoresis, suspension, electrochemical deposition, vapor deposition, VLS growth method (vapor-liquid-solid method) (VLS), ion track, melting process, interfacial polymerization, electrospinning, antisolvent-induced polymer precipitation, electrostatic spinning, catalytic synthesis, liquid phase synthesis, and "island in the sea" (see, e.g., Xiangwu Zhang, Ph.D., Xiangwu (January 1, 2014). Fundamentals of Fiber Science (1st Edition). Lancaster PA: DEStech Publications, Inc. p. 426. ISBN 978-1-60595-119-5). (Item 83) 83. The device of any one of items 24 to 82, wherein the nanostructure is prepared by combining the inner core and the outer surface to form the nanostructure. (Item 84) Item 84. The device of item 83, wherein the inner core and the outer surface are brought together in the presence of external energy for combination to form the nanostructure. (Item 85) 85. The device of claim 84, wherein the external energy is mechanical energy, acoustic energy, or thermal energy. (Item 86) 86. The device of any one of items 24 to 85, comprising a plurality of said nanostructures forming a nanostructure network. (Item 87) 87. The device according to claim 86, wherein the nanostructure network comprises a plurality of nanostructures according to any one of items 24 to 85 as components of the nanostructure network. (Item 88) 87. The device of claim 86, wherein the nanostructure network comprises at least two nanostructures of any one of items 24 to 85. (Item 89) 89. The device of claim 87 or 88, comprising multiple layers of said nanostructure network to form a nanoscaffold. (Item 90) 90. The device of claim 89, wherein the nanoscaffold comprises at least one layer of the nanostructure. (Item 91) 4. The device according to any one of items 1 to 3, wherein the cartridge or adsorbent comprises an entire surface including the cell membrane. (Item 92) The cartridge or sorbent may comprise: 1) a nanoparticle comprising the cell membrane; 2) a nanostructure (e.g., a nanofiber) comprising the cell membrane; 3) the entire surface including the cell membrane; The device according to any one of items 1 to 91, comprising at least two or all three of the following: (Item 93) 93. The device according to any one of items 1 to 92, wherein the cell membrane is derived from a blood cell, a tumor cell, a cancer cell, an immune cell, a stem cell, an endothelial cell, a neuronal cell, an exosome, a secretory vesicle and / or a synaptic vesicle. (Item 94) 94. The device of item 93, wherein the cell membrane is derived from a red blood cell, a platelet, a macrophage, a neutrophil and / or a neuron. (Item 95) 94. The device of item 93, wherein the cell membrane is derived from a macrophage. (Item 96) 94. The device of item 93, wherein the cell membrane is derived from macrophages and neutrophils. (Item 97) 94. The device of item 93, wherein the cell membranes are derived from red blood cells and platelets. (Item 98) 94. The device of item 93, wherein the cell membrane is derived from a red blood cell, a platelet, and a neuron. (Item 99) 99. The device according to any one of the preceding claims, having a length ranging from 0.01 m to 1 m (meter). (Item 100) 2.5× -5 m 2 (square meter) ~ approx. 0.01m 2 99. The device of any one of the preceding claims, having a cross-sectional surface area ranging from 100 mm to 150 mm. (Item 101) 101. The device according to any one of items 1 to 100, which is an extracorporeal blood purification (EBP) device. (Item 102) 102. The device according to any one of items 1 to 101, wherein the cell membranes are derived from different cell types. (Item 103) 103. A device assembly comprising at least two devices according to any of items 1 to 102, wherein the at least two devices are in fluid communication and comprise cartridges or adsorbents comprising cell membranes derived from different cell types. (Item 104) A method for removing or reducing a substance from a fluid (e.g., a fluid, blood or urine of a subject), the method comprising contacting the fluid (e.g., a fluid, blood or urine of a subject) ex vivo with a device comprising a cell membrane derived from a cell. (Item 105) The method according to item 104, comprising contacting a liquid (e.g., a liquid, blood or urine of a subject) with the device according to any one of items 1 to 102, or the device assembly according to item 103. (Item 106) 106. The method of claim 104 or 105, wherein the substance to be removed or reduced from a fluid (e.g., a fluid, blood or urine of a subject) is a waste product, a cytokine (e.g., a pro-inflammatory cytokine), and / or a toxin. (Item 107) 107. The method of claim 106, wherein the toxin is a viral, bacterial, fungal, plant and / or animal toxin. (Item 108) 108. The method according to any one of items 104 to 107, wherein the subject is a mammal. (Item 109) 109. The method of claim 108, wherein the mammal is a non-human mammal. (Item 110) 19. The method of claim 108, wherein the mammal is a human (e.g., a human patient). (Item 111) The method according to any one of items 104 to 110, which is used to substantially remove or reduce from a fluid (e.g., a fluid, blood or urine of a subject) all substances that target or attack target cells of the subject. (Item 112) 112. The method of claim 111, wherein the substance to be removed or reduced from the blood of the subject is substantially any pathological or virulence factor that targets or attacks target cells of the subject. (Item 113) 113. The method of claim 111 or 112, wherein the subject target cell and the cell from which the cell membrane is derived are of the same cell type. (Item 114) The method according to any one of items 104 to 113, which is used for hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF) or high flux dialysis (HFD). (Item 115) The method according to any one of items 104 to 113, which is used to treat or prevent renal failure, liver failure or sepsis in a subject. (Item 116) 114. The method according to any one of items 104 to 113, used to treat or prevent an infection, a severe infection and / or sepsis in a subject, wherein the cell membrane is derived from a macrophage. (Item 117) The method of any one of items 104 to 113, wherein the cell membrane is derived from a macrophage and / or a neutrophil, for use in treating or preventing an inflammatory disorder or a severe inflammatory disorder (e.g., rheumatoid arthritis or pancreatitis) in a subject. (Item 118) 114. The method of any one of items 104 to 113, wherein the cell membrane is derived from red blood cells and / or platelets, for use in treating or preventing an autoimmune disease (e.g., autoimmune anemia) in a subject. (Item 119) 114. The method according to any one of items 104 to 113, used to treat or prevent a chemical or biological attack in a subject, wherein the cell membrane is derived from a red blood cell, a platelet and / or a neuron. (Item 120) 114. The method of any one of items 104 to 113, used to treat or prevent animal envenomation (e.g., fatal animal envenomation) in a subject, wherein the cell membrane is derived from a red blood cell, a platelet, and / or a neuron. (Item 121) The method according to any one of Items 104 to 113, wherein the device according to Item 102 or the device assembly according to Item 103 is used. (Item 122) 122. The method of claim 121, used to remove or reduce a number of substances from a fluid (e.g., a subject's blood).

Claims

1. A device for extracorporeal detoxification comprising a cartridge or sorbent comprising cell membranes derived from cells, said device having a cross-sectional surface area ranging from about 2.5 x 10-5 m2 (square meters) to about 0.01 m2 (square meters), said cartridge or sorbent having a ratio between the surface area of ​​the cell membrane and the volume of the cartridge or sorbent ranging from about 1 m-1 to about 3 x 108 m-1.

2. The cartridge or sorbent is about 10 m －１ ~Approx. 3×10 ８ m －１ 2. The device of claim 1, having a ratio between the surface area of ​​the cell membrane and the volume of the cartridge or sorbent ranging from 0.1 to 1.

3. The device of claim 1 or 2, wherein the cartridge or sorbent comprises a nanoparticle comprising the cell membrane, a nanostructure comprising the cell membrane, an entire surface comprising the cell membrane, or a combination thereof.

4. The device of claim 3 , wherein the cell membrane of the nanoparticle comprises a plasma membrane or an intracellular membrane.

5. The device of claim 3 or 4, wherein the cell membrane of the nanoparticles is derived from a multicellular organism.

6. The device of any one of claims 3 to 5, wherein the nanoparticles further comprise a releasable cargo.

7. The device of any one of claims 3 to 6, wherein the nanoparticles are biocompatible or biodegradable.

8. the cartridge or sorbent comprises a nanostructure comprising the cell membrane; Optionally, the nanostructure comprises: a) an inner core comprising non-cellular material; and b) an outer surface comprising a cell membrane derived from a cell; wherein the nanostructure comprises: 1) having a first dimension having a first dimensional parameter ranging from about 1 nm to about 10 μm and a second dimension having a second dimensional parameter of at least about 11 nm; and / or 2) having a first dimension having a first dimensional parameter ranging from about 1 nm to about 10 μm, a second dimension having a second dimensional parameter, and a ratio of said second dimensional parameter to said first dimensional parameter of at least about 2; A device according to any one of claims 1 to 3.

9. The device of claim 8 , wherein the nanostructure further comprises a releasable cargo.

10. The device according to claim 8 or 9, wherein the nanostructures are configured as one-dimensional nanostructures or two-dimensional nanostructures.

11. 11. The device of claim 10, wherein the nanostructure further comprises a third dimension having a third dimensional parameter of at least about 11 nm and / or a ratio of the third dimensional parameter to the first dimensional parameter of at least about 10.

12. About 5×10 −5 m 2 to about 0.01 m ２ The device of any one of claims 1 to 11, having a cross-sectional surface area in the range of (m2).

13. The device according to any one of claims 1 to 12, which is an extracorporeal blood purification (EBP) device.

14. A device assembly comprising at least two devices according to any one of claims 1 to 13, wherein said at least two devices are in fluid communication and comprise cartridges or adsorbents comprising cell membranes derived from different cell types.

15. A device according to any one of claims 1 to 13 or a device assembly according to claim 14 for use in a method for removing or reducing a substance from a liquid, the method comprising contacting a liquid with the device or device assembly ex vivo.

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