Device containing cell membranes and uses thereof

Abstract

The present disclosure relates to devices, such as extracorporeal blood purification (EBP) devices, that include a cartridge or sorbent that includes cell-derived cell membranes. The present disclosure also relates to methods of using the devices or EBP devices to remove or reduce a substance (e.g., an undesirable substance) from a fluid (e.g., a subject's blood).

Description

[0001] I. Related Applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 963,465, filed January 20, 2020, the disclosure of which is incorporated herein by reference in its entirety for all purposes.

[0003] II. Technical Field

[0004] This disclosure relates to devices, such as extracorporeal blood purification (EBP) devices, which include a housing or adsorbent comprising a cell membrane derived from cells. This disclosure also relates to methods for removing or reducing substances (e.g., undesirable substances) from a fluid (e.g., the blood of a subject) using said devices or EBP devices.

[0005] III. Background Technology

[0006] Extracorporeal blood purification (EBP) is a therapeutic procedure in which a patient's blood is allowed to pass through a device designed to remove unwanted solutes, such as waste products, pro-inflammatory cytokines, and toxins. Devices used for EBP can be broadly classified into two categories: (1) molecular-size-based filtration, such as hemodialysis (HD), hemofiltration (HF), hemodialysis filtration (HDF), and high-flux dialysis (HFD); and (2) adsorption, such as 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 critical illnesses such as renal failure, liver failure, and sepsis.

[0007] However, existing technologies face significant drawbacks. (1) Devices based on filtration, convection, and diffusion use molecular weight as a cutoff value and cannot distinguish the biological characteristics of the filtrate. (2) Due to the limited infusion volume during convection and the limited membrane permeability during diffusion, convection and diffusion cannot achieve good clinical clearance rates for high molecular weight and hydrophobic molecules. (3) Devices based on physical adsorption, such as charcoal, are non-specific and cause harm by indiscriminately removing important molecules. (4) For specific adsorption, the selection of ligands that bind to toxins is limited and costly. For each target toxin, a specially prepared ligand is required, which is impractical for most diseases where the pathological or virulence factors are unknown.

[0008] There is a need for new devices or EBP devices and methods for using these devices or EBP devices to remove or reduce substances (e.g., unwanted substances) from a subject's fluids or blood, addressing the challenges of current devices and methods. This invention solves this problem and addresses the related needs in the art.

[0009] IV. Summary of the Invention

[0010] In one aspect, this disclosure provides an apparatus, such as an extracorporeal blood purification (EBP) device, which includes a housing or adsorbent comprising a cell membrane derived from cells.

[0011] In another aspect, this disclosure provides a device assembly comprising at least two of the aforementioned devices or EBP devices in fluid communication. The devices or EBP devices in the device assembly include a housing or adsorbent comprising a cell membrane derived from different cell types.

[0012] In another aspect, this disclosure provides a method for removing or reducing a substance (e.g., an undesirable substance) from a fluid (e.g., the blood of a subject), the method comprising contacting the fluid (e.g., the blood of a subject) in vitro with a device comprising a cell-derived cell membrane. In some embodiments, the method of the present invention comprises contacting the fluid (e.g., the blood of a subject) in vitro with a device or EBP device comprising a housing or adsorbent comprising a cell-derived cell membrane. In some embodiments, the method comprises contacting the fluid (e.g., the blood of a subject) with a device assembly comprising at least two of the aforementioned devices or EBP devices in fluid communication.

[0013] In some respects, this disclosure relates to U.S. Application No. 13 / 827,906, filed March 14, 2013 and published as US 2013 / 0337066 A1; International Application No. PCT / US2012 / 039411, filed May 24, 2012 and published as WO 2013 / 052167 A2; and International Application No. PCT / US2017 / 012342, filed January 5, 2017 and published as WO 2017 / 120342 A1. The contents of the above applications are incorporated herein by reference in their entirety.

[0014] V. Illustrations

[0015] Those skilled in the art will understand that the accompanying drawings described below are for illustrative purposes only. The drawings do not limit the scope of the invention in any way.

[0016] The patent or application documents contain at least one color drawing. The Patent Office will provide a copy of the patent or patent application publication with the color drawing upon request and upon payment of the necessary fees.

[0017] Figure 1 This demonstrates the use of cell membranes as a component for in vitro detoxification.

[0018] Figure 2Examples of packaging cell membranes to create “membrane cassettes” for in vitro detoxification are illustrated, including (A) cell membranes wrapped around nanofibers, (B) cell membranes spread on a plate for detoxification, (C) cell membranes forming vesicles or particles and embedded within a hydrogel for detoxification, and (D) cell membranes wrapped around magnetic particles for enrichment and separation during detoxification.

[0019] Figure 3 An exemplary device assembly is described, in which cell membrane cartridges are connected in series. Fluids, such as the blood of a subject, can be sequentially detoxified or have substances removed through the cell membrane cartridges.

[0020] VI. Detailed Description of the Invention

[0021] Unless otherwise stated, the present invention will be practiced using conventional techniques in nanotechnology, nanoengineering, molecular biology (including recombinant technology), microbiology, cell biology, biochemistry, immunology and pharmacology within the scope of the art. These techniques are well explained in the literature, for example, 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 (FMAusubel et al., eds., 1987, regularly updated); 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 (2012, Pharmaceutical Press and Philadelphia College of Pharmacy at the University of the Sciences).

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. All patents, applications, publications, and other publications mentioned herein are incorporated herein by reference in their entirety. If any definition set forth in this section contradicts or is inconsistent with a definition set forth in a patent, application, publication, or other publication incorporated herein by reference, the definition set forth in this section shall prevail over the definition incorporated herein by reference.

[0023] A. Definition

[0024] To facilitate understanding of this invention, many terms and abbreviations used herein are defined as follows:

[0025] When describing elements of the invention or its preferred embodiments, the articles “a,” “an,” “the,” and “the” are intended to indicate the presence of one or more elements. The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be other elements besides those listed.

[0026] The term "and / or" when used in a list of two or more items means that any one of the listed items can be used alone or in combination with any one or more of the listed items. For example, the expression "A and / or B" is intended to mean one or both of A and B, i.e., A alone, B alone, or a combination of A and B. The expression "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.

[0027] Cell membrane: As used herein, the term "cell membrane" refers to a biological membrane that serves as a selective barrier, either closed or open, within or around a cell or a viral particle, selectively permeable to ions and organic molecules, and controlling the movement of substances into and out of the cell. A cell membrane comprises a phospholipid monolayer or bilayer, and optionally associated proteins and carbohydrates. As used herein, a cell membrane refers to a membrane obtained from or derived from a naturally occurring biological membrane of a cell or organelle. As used herein, the term "naturally occurring" means existing in nature. As used herein, the term "derived from" refers to any subsequent modification of a natural membrane, such as isolating a cell membrane, producing a portion or fragment of a membrane, removing certain components from a membrane taken from a cell or organelle, and / or adding certain components, such as lipids, proteins, or carbohydrates, to a membrane taken from a cell or organelle. Membranes can be derived from naturally occurring membranes by any suitable method. For example, membranes can be prepared or isolated from cells, and prepared or isolated membranes can be combined with other substances or materials to form derived membranes. In another example, cells can be recombinantly engineered to produce “non-natural” substances incorporated into their membranes in vivo, and cell membranes can be prepared from or separated from cells to form derived membranes.

[0028] In various embodiments, cell membranes covered with single or multiple layers of nanoparticles or nanostructures can be further modified with other saturated or unsaturated lipid components, such as cholesterol, free fatty acids, and phospholipids, and may also include endogenous or added proteins and carbohydrates, such as cell surface antigens. In this case, excess of other lipid components can be added to the membrane wall, which will detach until the concentration in the membrane wall reaches equilibrium, which may depend on the nanoparticle environment. The membrane may also contain other agents that may or may not increase the activity of the nanoparticles. In other embodiments, functional groups such as antibodies and aptamers can be added to the outer surface of the membrane to enhance site targeting, such as targeting cell surface epitopes found in cancer cells. The nanoparticle or nanostructure membrane may also contain biodegradable particles, including but not limited to cationic nanoparticles of gold, silver, and synthetic nanoparticles.

[0029] Synthetic or artificial membranes: As used herein, the terms "synthetic membrane" or "artificial membrane" refer to artificial membranes made from organic materials such as polymers and liquids, as well as inorganic materials. Various synthetic membranes are well known in the art.

[0030] Nanoparticles: In some embodiments, the term "nanoparticle" as used herein refers to a nanostructure, particle, vesicle, or fragment thereof having at least one aspect (e.g., height, length, width, or diameter) between about 1 nm and 10 nm. For systematic use, an average diameter of about 50 nm to about 500 nm, or 100 nm to 250 nm, is preferred. The term "nanostructure" includes, but is not limited to, particles and engineered features. Particles and engineered features may have, for example, regular or irregular shapes. Such particles are also called nanoparticles. Nanoparticles may be composed of, or implemented using, organic or other materials. Nanoparticles may be composed of, or implemented using, organic or other materials. Nanoparticles may be composed of, or implemented using, porous particles. Nanoparticle layers may be implemented using a single layer of nanoparticles or using a layer having nanoparticle aggregates. In some embodiments, nanoparticles comprise or consist of internal compartments (or cores) covered by an outer surface (or shell) comprising a membrane as discussed herein. This disclosure contemplates any nanoparticles now known and hereafter developed that can be encapsulated in the membranes described herein.

[0031] In some embodiments, the term "nanostructure" as used herein refers to a structure having at least one dimension (e.g., height, length, width, or diameter) between about 1 nm and about 10 μm, such as nanofibers, nanotubes, nanowires, or nanosheets. A "nanostructure" can be a one-dimensional or two-dimensional nanostructure. The size parameters of the second and / or third dimensions may or may not be within the size 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, nanofibers, nanotubes, nanowires, or nanosheets and engineered features. Nanostructures and engineered features may have, for example, regular or irregular shapes. Nanoparticles may be composed of inorganic, organic, or other materials, or alternatively, porous materials. Nanostructure layers can be implemented using nanostructures in a monolayer or layers having aggregates of nanostructures. In some embodiments, the nanostructure has a core covered by an outer surface comprising a cell-derived membrane. The present invention contemplates any nanostructures now known and hereafter developed that can be coated with the membranes described herein.

[0032] Pharmaceutical activity: As used herein, the term "pharmaceutical activity" refers to the beneficial biological activity of a substance on living matter, particularly on human cells and tissues. A "pharmaceutical active agent" or "drug" is a substance that has pharmaceutical activity, while a "pharmaceutical active ingredient" (API) is the pharmaceutically active substance in a drug.

[0033] Pharmaceutically acceptable: As used herein, “pharmaceutically acceptable” means, in addition to other preparations that are safe for use in animals, preparations approved by a U.S. federal or state regulatory agency or listed in the United States Pharmacopeia, other recognized pharmacopoeias, and especially for use in humans and / or non-human mammals.

[0034] Pharmaceutically Acceptable Salt: As used herein, the term "pharmaceutically acceptable salt" refers to an acid or base addition salt of a compound such as a polydrug conjugate as described in this disclosure. A pharmaceutically acceptable salt is any salt that retains the activity of the parent nanoparticle or compound and does not have any harmful or adverse effects on the subject or administration environment. Pharmaceutically acceptable salts may be derived from amino acids, including but not limited to cysteine. Methods for preparing 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, "pharmaceutically acceptable salt" is intended to mean a salt of a free acid or base of a nanoparticle or compound as described herein that is non-toxic, biologically tolerable, or biologically suitable for administration to a subject. See, generally, Berge et al., J. Pharm. Sci., 1977, 66, 1-19. Preferred pharmaceutically acceptable salts are those that are pharmacologically effective and suitable for contact with the tissues of a subject without excessive toxicity, irritation, or anaphylactic reactions. 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 accordingly react with a variety of inorganic or organic bases and inorganic and organic acids to form pharmaceutically acceptable salts.

[0035] Examples of pharmaceutically acceptable salts include sulfates, metasulfites, bisulfites, sulfites, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, hexanoates, heptaesters, propynyl esters, oxalates, malonates, succinates, octanoates, sebacic acid esters, fumarates, maleates, butyrates... 1,4-Dioster, hexyn-1,6-Dioster, benzoate, chlorobenzoate, methyl benzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, sulfonate, methanesulfonate, propanesulfonate, benzenesulfonate, xylenesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, [γ]-hydroxybutyrate, glycolate, tartrate, and mandelate.

[0036] Pharmaceutically acceptable carriers: As used herein, the term "pharmaceuticalally acceptable carrier" refers to excipients, diluents, preservatives, solubilizers, emulsifiers, adjuvants, and / or carriers, nanoparticles, or compounds (e.g., multidrug conjugates) administered together with the drug. Such carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc., polyethylene glycol, glycerol, propylene glycol, or other synthetic solvents. Antimicrobial agents, such as benzyl alcohol or methylparaben; antioxidants, such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; and agents used to regulate tension, such as sodium chloride or glucose, can also be carriers. Methods for producing compositions combined with carriers are known to those skilled in the art. In some embodiments, the term "pharmaceuticalally acceptable carrier" is intended to include any and all solvents, dispersion media, coatings, isotonic agents, and absorption delay agents compatible with drug administration. The use of such media and agents for pharmaceutically active substances is well known in the art. See, for example, Remington, The Science and Practice of Pharmacy, 20'ed. (Lippincott, Williams & Wilkins 2003). This use in the composition will be considered unless any conventional medium or agent is incompatible with the active compound.

[0037] Phospholipids: As used herein, the term "phospholipid" refers to any of a large number of lipids comprising a diglyceride, a phosphate group, and a simple organic molecule such as choline. Examples of phospholipids include, but are not limited to, phosphatidic acid (phosphatidylcholine) (PA), phosphatidylethanolamine (cephalin) (PE), phosphatidylcholine (lecithin) (PC), phosphatidylserine (PS), and phosphatidylinositol, which includes, but is not limited to, phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), phosphatidylinositol diphosphate (PIP2), and phosphatidylinositol triphosphate (P1P3). Other examples of PC include DDPC, DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DRPC, and DEPC as defined in the art.

[0038] Therapeutic effective amount: As used herein, the term "therapeutic effective amount" refers to an amount that, when administered to a particular subject or in vitro to the subject's bodily fluids (e.g., the subject's blood), would have the desired therapeutic effect given the nature and severity of the subject's disease or condition, such as an amount that would cure, prevent, suppress, or at least partially suppress or partially prevent the target disease or condition. In some embodiments, the term "therapeutic effective amount" or "effective amount" refers to an amount that, when administered alone or in combination with another therapeutic agent to cells, tissues, or a subject, effectively prevents or improves a disease or condition such as hemolytic disease and its progression. A therapeutic effective amount also refers to an amount sufficient to improve symptoms, such as the treatment, cure, prevention, or improvement of an associated medical condition, or an amount sufficient to increase the rate of treatment, cure, prevention, or improvement of such conditions. When applied to a single active ingredient administered alone, the therapeutic effective amount refers to that ingredient alone. When applied to a combination, the therapeutic effective amount refers to the combined amount of active ingredients that result in the therapeutic effect, whether administered in combination, continuously, or concurrently.

[0039] "Treatment" or "treatment" refers to medical treatment in which the goal is to slow (alleviate) a target pathological condition or symptom or to prevent recurrence of the condition, if a cure is not possible. A subject is considered successfully "cured" if, after receiving a therapeutic dose of the treatment agent, the subject exhibits an observable and / or measurable reduction or disappearance of one or more signs and symptoms of a specific disease. The patient may also feel a reduction in the signs or symptoms of the disease. Stable condition is also considered a sign of treatment. In some embodiments, treatment with the treatment agent is intended to effectively result in the patient being disease-free for 3 months, preferably 6 months, more preferably 1 year, or even more preferably 2 years or more after treatment. These parameters used to assess successful treatment and improvement of the disease can be readily measured using routine procedures familiar to physicians with appropriate skills in the art.

[0040] As used in this article, "preventative" treatment is intended to indicate the delay of the development of a disease, its symptoms, or medical symptoms; to suppress the possible onset of symptoms; or to reduce the risk of the development or recurrence of a disease or its symptoms. "Cure" treatment includes reducing the severity of an existing disease, its symptoms, or its condition, or inhibiting its worsening.

[0041] The term "combination" refers to a fixed combination in a single dose unit or a kit for combination administration, wherein the nanoparticles or compounds and the combination chaperone (e.g., another drug as explained below, also referred to as a "therapeutic agent" or "synergist") can be administered simultaneously or separately at time intervals, particularly where these time intervals allow the combination chaperone to exhibit cooperation, such as a synergistic effect. As used herein, the terms "co-administration" or "combination administration," etc., are intended to include administering selected combination chaperones to a single subject (e.g., a patient) in need and are intended to include treatment regimens in which these agents are not necessarily administered via the same route of administration or simultaneously. As used herein, the term "drug combination" refers to a product resulting from a mixture or combination of more than one active ingredient and includes fixed and non-fixed combinations of active ingredients. The term "fixed combination" refers to an active ingredient, such as nanoparticles or compounds, and a combination chaperone, both administered simultaneously to a patient in a single entity or dose. The term "non-fixed combination" refers to the administration of an active ingredient, such as nanoparticles or compounds, and a combination chaperone, both as separate entities, together, simultaneously, or sequentially, without a specific time limit, wherein such administration provides therapeutically effective levels of both portions or compounds in the patient's body. The latter also applies to cocktail therapies, such as the administration of three or more active ingredients.

[0042] It should be understood that the aspects and embodiments of the invention described herein include aspects and embodiments that are “composed of” and / or “substantially composed of”.

[0043] Throughout this disclosure, various aspects of the invention are presented in a scope format. It should be understood that this scope format is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of the invention. Therefore, it should be assumed that the description of scope specifically discloses all possible sub-scopes and the individual numerical values ​​within those scopes. For example, a description of a scope such as 1 to 6 should be considered to have specifically disclosed sub-scopes, such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., and individual numbers within that scope, such as 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the scope.

[0044] As used herein, a subject in need refers to an animal, a non-human mammal, or a human. As used herein, “animal” includes pets, farm animals, commercial animals, sporting animals, and laboratory animals, such as cats, dogs, horses, cattle, cows, pigs, donkeys, sheep, lambs, goats, mice, rabbits, chickens, ducks, geese, and primates, including monkeys and chimpanzees.

[0045] Other objects, advantages and features of the invention will become apparent from the following description taken in conjunction with the accompanying drawings.

[0046] B. A device having a housing or adsorbent, wherein the housing or adsorbent has a cell membrane.

[0047] In one aspect, this disclosure provides an apparatus, such as an extracorporeal blood purification (EBP) device, which includes a housing or adsorbent having a cell membrane derived from cells.

[0048] In this device, the container or adsorbent can have any suitable ratio between the surface area of ​​the cell membrane and the volume of the container or adsorbent. In some embodiments, the container or adsorbent can have a ratio between the surface area of ​​the cell membrane and the volume of the container or adsorbent ranging from about 1 m². -1 Approximately 3X10 8 m -1 The ratio, for example, approximately 1m -1 10m -1 100m -1 1,000m -1 1X10 4 m -1 1X10 5 m -1 1X10 6 m -1 1X10 7 m -1 1X10 8 m -1 3X10 8 m -1 , or any of its subranges.

[0049] In this device, the housing or adsorbent may have a cell membrane derived from any suitable form of cell. For example, in this device, the housing or adsorbent may comprise: nanoparticles containing a cell membrane, nanostructures containing a cell membrane (such as nanofibers), an intact surface containing a cell membrane, or a combination thereof.

[0050] In some embodiments, in this device, the housing or adsorbent comprises nanoparticles comprising cell membranes. Any suitable nanoparticles may be used in this device. For example, in this device, the housing or adsorbent may comprise nanoparticles comprising: a) a core comprising non-cellular material; and b) an outer surface comprising a cell membrane derived from a cell. Other suitable or exemplary nanoparticles described and / or claimed in US 2013 / 337066 A1 and WO 2013 / 052167 A2 may also be used.

[0051] In some embodiments, the housing or adsorbent in this device comprises a nanostructure (e.g., nanofibers) containing a cell membrane. Any suitable nanostructure or nanofiber can be used in this device.

[0052] For example, in this device, the housing or adsorbent may comprise a nanostructure comprising: a) a core containing non-cellular material; b) an outer surface comprising a cell membrane derived from a cell, wherein the nanostructure: 1) has a first dimension and a second dimension, the first dimension parameter ranging from about 1 nm to about 10 μm, and the second dimension having a second dimension parameter of at least about 11 nm; and / or 2) has a first dimension having a first dimension parameter ranging from about 1 nm to about 10 μm, and a second dimension having a second dimension parameter, and the ratio between the second dimension parameter and the first dimension parameter is at least about 2. Other suitable or exemplary nanostructures or nanofibers described and / or claimed in WO2017 / 120342A1 and the article by Wansong Chen et al., "Coating nanofiber scaffolds with beta cell membrane to promote cell proliferation and function," Nanoscale, may also be used. 8 :10364–10370(2016).

[0053] In some embodiments, in this device, the housing or adsorbent comprises an intact surface having a cell membrane. The cell membrane can be placed on the intact surface in any suitable manner. For example, the cell membrane can be coated or spread on the intact surface. In another example, the cell membrane can be placed using the method or process described by 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)) is placed on the complete surface.

[0054] In some embodiments, the housing or adsorbent in this device comprises at least two of the following: 1) nanoparticles containing a cell membrane; 2) nanostructures containing a cell membrane, such as nanofibers; 3) an intact surface containing a cell membrane. For example, in this device, the housing or adsorbent may comprise: nanoparticles containing a cell membrane and nanostructures containing a cell membrane, such as nanofibers; nanoparticles containing a cell membrane and an intact surface containing a cell membrane; or nanostructures containing a cell membrane, such as nanofibers; and an intact surface containing a cell membrane. In some embodiments, the housing or adsorbent in this device comprises: 1) nanoparticles containing a cell membrane; 2) nanostructures containing a cell membrane, such as nanofibers; 3) an intact surface containing a cell membrane.

[0055] In this device, the housing or adsorbent may comprise any suitable cell membrane. In some embodiments, the housing or adsorbent may comprise a plasma membrane or intracellular membrane derived from a single cell (e.g., bacteria or fungi) or a multicellular organism (e.g., plant, animal, non-human mammal, vertebrate, or human). In some embodiments, the housing or adsorbent may comprise 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 this device, the housing or adsorbent may comprise 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 this device, the housing or adsorbent may comprise a combination or fusion of a naturally occurring cell membrane, a modified cell membrane, and a synthetic membrane.

[0056] Cell membranes can be modified in any suitable manner. For example, in the device of the present invention, the housing or adsorbent may contain a cell membrane having altered or enhanced hormone levels (e.g., cholesterol) and / or altered or enhanced lipid levels (e.g., sphingomyelin). (See, for example, US 2015 / 0157570 A1.) In some embodiments, in this device, the housing or adsorbent may contain a cell membrane having altered or enhanced cholesterol and sphingomyelin levels.

[0057] In various embodiments, the cell membrane in this device may be further modified to be saturated or unsaturated by other lipid components (e.g., cholesterol, free fatty acids, and phospholipids), and may also contain endogenous or added proteins and carbohydrates, such as cell surface antigens. In this case, excess of other lipid components may be added to the membrane wall until the concentration in the membrane wall reaches equilibrium, at which point the membrane wall will detach, which may depend on the nanoparticle or nanostructure environment. The membrane may also contain other reagents that may or may not increase the activity of this device. In other instances, functional groups such as antibodies and aptamers may be added to the outer surface of the membrane to enhance site targeting, such as to cell surface epitopes. The cell membrane in this device may also contain biodegradable particles, cationic nanoparticles, including but not limited to gold, silver, and synthetic nanoparticles. (See, for example, WO 2017 / 120342 A1.)

[0058] In some embodiments, the cartridge or adsorbent in this device comprises cell membranes, secretory vesicles, and / or synaptic vesicles derived from blood cells, tumor cells, cancer cells, immune cells, stem cells, endothelial cells, neurons, or exogenous bodies. In some embodiments, the cartridge or adsorbent in this device comprises cell membranes derived from erythrocytes, platelets, macrophages, neutrophils, and / or neurons. In some embodiments, the cartridge or adsorbent in this device has a cell membrane derived from macrophages. In some embodiments, the cartridge or adsorbent in this device comprises cell membranes derived from macrophages and neutrophils. In some embodiments, the cartridge or adsorbent in this device comprises cell membranes derived from erythrocytes and platelets. In some embodiments, the cartridge or adsorbent in this device comprises cell membranes derived from erythrocytes, platelets, and neurons.

[0059] This device can have any suitable size, such as a suitable length and cross-sectional surface area. In some embodiments, the device of the present invention can have a length ranging from 0.01m to 1m, for example, about 0.01m, 0.02m, 0.03m, 0.04m, 0.05m, 0.06m, 0.07m, 0.08m, 0.09m, 0.1m, 0.2m, 0.3m, 0.4m, 0.5m, 0.6m, 0.7m, 0.8m, 0.9m, 1m or any subrange thereof. In some embodiments, this device can have a length ranging from 2.5 x 1m. -5 m 2 (square meters) to approximately 0.01m 2 The cross-sectional surface area (in square meters), for example, approximately 2.5 x 1. -5 m 2 5X1 -5 m 2 1X1 -4 m2 1X1 -3 m 2 0.01m 2 or any of its subranges.

[0060] This device can have any suitable shape. For example, the device can be cylindrical, with the housing or adsorbent located or contained within a tube. In another example, the device can be planar, with the housing or adsorbent existing in a planar form or on a plane.

[0061] This device can be configured for any suitable purpose or use. For example, this device can be configured as an extracorporeal blood purification (EBP) device.

[0062] In this device, the housing or adsorbent may contain cell membranes derived from any suitable type or number of cells. In some embodiments, the housing or adsorbent contains cell membranes derived from a single type of cell. In some embodiments, the housing or adsorbent contains cell membranes derived from different types of cells.

[0063] In another aspect, this disclosure provides a device assembly comprising at least two of the aforementioned devices, wherein the at least two devices are in fluid communication and include a housing or adsorbent having a cell membrane derived from different types of cells. For example, the device assembly may include 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50 or more devices in series (or sequentially) in fluid communication.

[0064] C. Methods for removing or reducing substances from liquids

[0065] In another aspect, this disclosure provides a method for removing or reducing a substance from a liquid (e.g., a liquid obtained from a subject), the method comprising contacting the liquid (e.g., a liquid obtained from a subject) in vitro with a device having a cell membrane derived from a cell.

[0066] This method can be used to remove or reduce substances from any suitable liquid, such as any suitable liquid obtained from a subject. For example, the method of the present invention can be used to remove or reduce substances, such as undesirable substances, from the blood or urine of a subject. In some embodiments, this disclosure provides a method for removing or reducing substances (e.g., undesirable substances) from the blood of a subject, the method comprising contacting the subject's blood outside the body with a device having a cell membrane derived from cells.

[0067] Any suitable device or device component can be used in this method. In some embodiments, the method includes contacting a liquid (e.g., a liquid obtained from a subject, blood, or urine) with the aforementioned device or device component.

[0068] This method can be used to remove or reduce any suitable unwanted substances from fluids, such as any suitable fluids, blood, or urine obtained from a subject. For example, this method can be used to remove or reduce waste products, cytokines (e.g., pro-inflammatory cytokines), and / or toxins from fluids, such as any suitable fluids, blood, or urine obtained from a subject. This method can be used to remove or reduce any suitable type of toxins, such as viral, bacterial, fungal, plant, and / or animal toxins.

[0069] This method can be used to remove or reduce any suitable unwanted substance from the liquid of any suitable object. For example, the object is a mammal. In some embodiments, the mammal is a non-human mammal. In some embodiments, the mammal is a human, such as a human patient.

[0070] This method can be used to remove or reduce unwanted substances from liquids to a suitable or desirable degree. For example, this method can be used to substantially remove or reduce all substances targeting or attacking target cells of a subject from their fluids or blood. In some embodiments, the method of the present invention can be used to substantially remove about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or more of substances targeting or attacking target cells of a subject from their fluids or blood. In another example, this method can be used to substantially remove or reduce all pathological or toxicological factors targeting or attacking target cells of a subject from their fluids or blood. In some embodiments, the method of the present invention can be used to substantially remove about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or more of pathological or toxicological factors targeting or attacking target cells of a subject from their fluids or blood.

[0071] In some implementations, the target cells and cell membrane-derived cells of the subject are the same type of cell. In other implementations, the target cells and cell membrane-derived cells of the subject are different types of cells.

[0072] This method can be used for any suitable purpose or use. In some embodiments, this method is used for hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), or high-flux dialysis (HFD). In some embodiments, this method is used to treat or prevent renal failure, liver failure, or sepsis in a subject. In some embodiments, this method is used to treat or prevent infection, severe infection, and / or sepsis in a subject, and wherein the cell membrane is derived from macrophages. In some embodiments, this method is used to treat or prevent inflammatory diseases or severe inflammatory diseases in a subject, such as rheumatoid arthritis or pancreatitis, and wherein the cell membrane is derived from macrophages and / or neutrophils. In some embodiments, this method is used to treat or prevent autoimmune diseases in a subject, such as autoimmune anemia, and wherein the cell membrane is derived from erythrocytes and / or platelets. In some embodiments, this method is used to treat or prevent chemical or biological weapon attacks in a subject, and wherein the cell membrane is derived from erythrocytes, platelets, and / or neurons. In some implementations, this method is used to treat or prevent animal venom, such as deadly animal venom, in a subject, and wherein the cell membrane is derived from red blood cells, platelets, and / or neurons.

[0073] This method may use any suitable number of devices or device components. In some embodiments, this method uses a single device or device component. In some embodiments, this method uses multiple devices or device components. In some embodiments, this method uses multiple devices or device components to remove or reduce multiple substances from a liquid (e.g., a subject's fluids or blood). In some cases, each of the multiple devices or device components is used to remove or reduce a specific (or a specific type) substance from the liquid (e.g., a subject's fluids or blood).

[0074] D. Exemplary Model

[0075] In some embodiments, the present invention uses membranes derived from living cells as active ingredients to selectively capture and remove substantially all or all pathological or toxicological factors that would otherwise attack cells due to their biological activity. 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 displays the exact same antigenic spectrum as the source cell. Therefore, the device can remove toxins without identifying individual toxin components. (3) By acting as a proxy for target cells, these devices can capture toxins by precisely mapping the complexity and diversity of disease pathology. (4) The derivation of cell membranes from different cell types follows similar manufacturing processes, which facilitates or ensures the scalability of the technology.

[0076] In some implementations, in order to fabricate the membrane cartridge, the cell membrane will be combined with other engineering methods (such as nanotechnology) to fill the filter / cartridge. Figure 2 By combining with nanotechnology, the surface area to volume ratio of materials will be significantly improved. This will allow for the encapsulation of large quantities of membranes into small volumes for detoxification. For example, membranes can be formulated as nanoparticles. In some cases, nanoparticles can be embedded in hydrogels for retention, or wrapped around magnetic particles for enrichment and separation. Membranes can also be spread onto entire surfaces or fibers to allow fluids to pass through and capture toxins.

[0077] In some implementations, for therapeutic purposes, specific cell types can be selected for membrane derivatization and applied to treat different diseases (see, for example, Table 1). For instance, membranes derived from macrophages can be used to treat severe infections and sepsis. Membranes derived from neutrophils can be used to treat severe inflammatory diseases such as rheumatoid arthritis or pancreatitis. Membranes derived from erythrocytes (RBCs) can be used to treat severe autoimmune diseases such as autoimmune anemia. Membranes derived from erythrocytes or neurons can be used to treat chemical and biological weapons attacks or deadly animal venom.

[0078] Table 1. Potential diseases that can be treated via membrane-based in vitro detoxification and potential membrane-derived therapies

[0079] disease Potential membrane source Severe infection and sepsis macrophages Severe inflammatory diseases Macrophages, neutrophils Severe autoimmune diseases Red blood cells, platelets Chemical and biological weapons attacks Red blood cells, platelets, and neurons Deadly animal venom Red blood cells, platelets, and neurons

[0080] In some implementations, given the complexity of the disease, membranes from multiple cells can be used. In this case, the membrane capsules can be connected in series, and fluids can be detoxified sequentially. Figure 3 ).

Claims

1. A device for in vitro detoxification, comprising a housing or an adsorbent having a cell membrane derived from cells, wherein... The container or adsorbent has a surface area on the cell membrane and a volume of the container or adsorbent ranging from [value missing]. to The ratio.

2. The apparatus according to claim 1, characterized in that, The housing or adsorbent has a range between the surface area of ​​the cell membrane and the volume of the housing or adsorbent. to The ratio.

3. The apparatus according to claim 1 or 2, characterized in that, The housing or adsorbent comprises: nanoparticles containing cell membranes, nanostructures containing cell membranes, an intact surface containing the cell membrane, or a combination thereof.

4. The apparatus according to claim 1, characterized in that, The box or adsorbent contains nanoparticles, and the nanoparticles contain the cell membrane.

5. The apparatus according to claim 4, characterized in that, The nanoparticles comprise: a) A core containing non-cellular material; and b) Includes the outer surface of the cell membrane derived from the cell.

6. The apparatus according to claim 5, characterized in that, The core of the nanoparticle supports the outer surface of the nanoparticle.

7. The apparatus according to claim 5 or 6, characterized in that, The core comprises a biocompatible or synthetic material selected from poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polylysine, and polyglutamic acid.

8. The apparatus according to claim 3, characterized in that, The cell membrane of the nanoparticles has a plasma membrane or an intracellular membrane.

9. The apparatus according to claim 3, characterized in that, The cell membranes of the nanoparticles are derived from multicellular organisms.

10. The apparatus according to claim 5, characterized in that, The nanoparticles also contain a releasable loading material.

11. The apparatus according to claim 10, characterized in that, The releasable load is located within or on the core, between the core and the outer surface, or within or on the outer surface.

12. The apparatus according to claim 10 or 11, characterized in that, The release of the releasable load is triggered by contact between the nanoparticles and the liquid.

13. The apparatus according to claim 10, characterized in that, The releasable loading is a therapeutic agent, a preventive agent, a diagnostic agent or marker, a prognostic agent, a barrier agent, or a combination thereof.

14. The apparatus according to claim 10, characterized in that, The releasable loading material is polymer particles or inorganic particles.

15. The apparatus according to claim 3, characterized in that, The nanoparticles have a diameter of about 10 nm to about 10 μm.

16. The apparatus according to claim 3, characterized in that, The nanoparticles are essentially devoid of the cellular components from which cell membranes originate.

17. The apparatus according to claim 3, characterized in that, The cell membrane of the nanoparticles has a plasma membrane derived from red blood cells and the nanoparticles are substantially free of hemoglobin.

18. The apparatus according to claim 3, characterized in that, The nanoparticles substantially maintain the natural structural integrity or activity of the cell membrane or its components.

19. The device according to claim 3, wherein the nanoparticles are biocompatible or biodegradable.

20. The apparatus according to claim 5, characterized in that, The core of the nanoparticle contains PLGA and the outer surface contains a plasma membrane derived from red blood cells.

21. The apparatus according to claim 20, characterized in that, The core of the nanoparticle contains PLGA, and the outer surface contains a plasma membrane derived from human red blood cells.

22. The apparatus according to claim 3, characterized in that, The nanoparticles are substantially lacking in immunogenicity to species or objects from which the cell membrane is derived.

23. The apparatus according to claim 5 or 20, characterized in that, The outer surface has a naturally occurring cell membrane and also has a modified cell membrane and / or a synthetic membrane.

24. The apparatus according to claim 1, characterized in that, The box or adsorbent contains a nanostructure, and the nanostructure contains the cell membrane.

25. The apparatus according to claim 24, characterized in that, The nanostructure includes: a) A core containing non-cellular material; and b) Includes the outer surface of the cell membrane derived from the cell; The nanostructures mentioned above: 1) Having a first dimension and a second dimension, wherein the first dimension parameter ranges from about 1 nm to about 10 µm, and the second dimension has a second dimension parameter of at least about 11 nm; and / or 2) A first dimension having a first dimension parameter ranging from about 1 nm to about 10 µm, and a second dimension having a second dimension parameter, wherein the ratio between the second dimension parameter and the first dimension parameter is at least about 2.

26. The apparatus according to claim 25, characterized in that, The core of the nanostructure includes inorganic substances, organic substances, or their aggregates or complexes.

27. The apparatus of claim 26, wherein the inorganic material in the nanostructure core comprises: Superconducting materials, metallic materials, semiconductor materials, insulating materials, ions, or coordination complexes.

28. The apparatus according to claim 26, characterized in that, The organic material in the core of the nanostructure is selected from amino acids, peptides, proteins, nucleosides, nucleotides, oligonucleotides, nucleic acids, vitamins, carbohydrates, lipids, or aggregates or complexes thereof.

29. The apparatus according to any one of claims 25-28, characterized in that, The non-cellular material of the core of the nanostructure includes polymers.

30. The apparatus according to claim 29, characterized in that, The polymer is selected from poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polylysine, polyglutamic acid, and hydrophobic polymers that curl up when transferred from an organic solvent to an aqueous phase.

31. The apparatus according to claim 24, characterized in that, The core of the nanostructure contains biocompatible materials and / or synthetic materials.

32. The apparatus according to claim 24, characterized in that, The core of the nanostructure supports the outer surface of the nanostructure.

33. The apparatus according to claim 24, characterized in that, The cell membrane includes the plasma membrane or the intracellular membrane.

34. The apparatus according to claim 24, characterized in that, The cell membrane is derived from multicellular organisms.

35. The apparatus according to claim 34, characterized in that, The multicellular organisms are animals, plants, or filamentous fungi.

36. The apparatus according to claim 35, characterized in that, The animal in question is either an invertebrate or a vertebrate.

37. The apparatus according to claim 36, characterized in that, The vertebrates are fish, amphibians, reptiles, birds, or mammals.

38. The apparatus according to claim 37, characterized in that, The mammals mentioned are non-human mammals.

39. The apparatus according to claim 38, characterized in that, The non-human mammals mentioned are rodents, pterygians, tufted animals, primates, cetaceans, or even-toed ungulates or carnivores.

40. The apparatus according to claim 37, characterized in that, The mammal in question is a human.

41. The apparatus according to claim 25, characterized in that, The nanostructure also includes a releasable loading material.

42. The apparatus according to claim 41, characterized in that, The releasable load is located within or on the core, between the core and the outer surface, or within or on the outer surface.

43. The apparatus according to claim 41 or 42, characterized in that, The release of the releasable load is triggered by contact between the nanostructure and the liquid.

44. The apparatus according to claim 41, characterized in that, The releasable loading material is a therapeutic agent, a preventive agent, a diagnostic agent or marker, a prognostic agent, a barrier agent, or a combination thereof.

45. The apparatus according to claim 41, characterized in that, The releasable loading material is polymer particles or inorganic particles.

46. ​​The apparatus according to claim 24, characterized in that, The nanostructure essentially lacks the cellular components from which the cell membrane originates.

47. The apparatus according to claim 24, characterized in that, The cell membrane of the nanostructure includes a plasma membrane derived from red blood cells, and the nanostructure is substantially free of hemoglobin.

48. The apparatus according to claim 24, characterized in that, The nanostructure essentially maintains the natural structural integrity or activity of the cell membrane or its components.

49. The apparatus according to claim 24, characterized in that, The nanostructure is biocompatible or biodegradable.

50. The apparatus according to claim 25, characterized in that, The core of the nanostructure contains PLGA and the outer surface contains a plasma membrane derived from red blood cells.

51. The apparatus according to claim 24, characterized in that, The nanostructure is substantially lacking in immunogenicity for the species or subjects from which the cell membrane is derived.

52. The apparatus according to claim 24, characterized in that, The outer surface of the nanostructure contains naturally occurring cell membranes and also contains modified cell membranes and / or synthetic membranes.

53. The apparatus according to claim 52, characterized in that, The naturally occurring cell membrane, the modified cell membrane, and / or the synthetic membrane contain modifiers.

54. The apparatus according to claim 53, characterized in that, The modification is a physical modification, a chemical modification, or a biological modification.

55. The apparatus according to claim 25, characterized in that, The second dimension parameter is at least about 11 nm, and the ratio between the second dimension parameter and the first dimension parameter is at least about 10.

56. The apparatus according to claim 25, characterized in that, The second dimension parameter is at least about 1 mm.

57. The apparatus according to claim 25, characterized in that, The ratio between the second dimension parameter and the first dimension parameter is at least about 1,000.

58. The apparatus according to claim 56 or 57, characterized in that, The second dimension parameter is at least about 1 mm, and the ratio between the second dimension parameter and the first dimension parameter is at least about 1,000.

59. The apparatus according to claim 24, characterized in that, The nanostructure is configured as a one-dimensional nanostructure.

60. The apparatus of claim 25, wherein the nanostructure is configured as nanofibers, nanotubes, or nanowires.

61. The apparatus according to claim 60, characterized in that, The second dimensional parameter of the nanofiber, nanotube, or nanowire is at least about 1 cm, 1 m, or 10 m.

62. The apparatus according to claim 59, characterized in that, The one-dimensional nanostructure has a shape that includes straight line segments, a polygonal shape that includes a specific number of sides, a shape that includes arcs, or a shape that does not include arcs.

63. The apparatus according to claim 62, characterized in that, The shape including the line segment is selected from the group consisting of: balbis, concave polygon, constructible polygon, convex polygon, cyclic polygon, isoangular polygon, equilateral polygon, Penrose tile, polymorph, regular polygon, simple polygon, and tangent polygon.

64. The apparatus according to claim 62, characterized in that, The shape, including polygons with a specific number of sides, is selected from the group consisting of: unilateral, diagonal, triangle, quadrilateral, pentagon, hexagon, heptagon, octagon, nonagon, decagon, dodecagon, hexagonal, icosahedron, and star polygon.

65. The apparatus according to claim 62, characterized in that, The shape including the arc is selected from the group consisting of: ring, arbelos, circle, sector, segment, crescent, Indalo, lens, half-moon, Reuleaux polygon, Salinon, semicircle, tomahawk, and trident.

66. The apparatus according to claim 62, characterized in that, The shape excluding the arc is selected from the group consisting of: Archimedean spiral, stellate line, triangular line, ellipse, heart shape, cartogonal shape, zygotic line, oval shape, hyperellipse, yin-yang symbol and tomoe.

67. The apparatus according to claim 59, characterized in that, The one-dimensional nanostructure has a shape selected from the group consisting of: square, rectangle, triangle, disk, and other regular or irregular shapes.

68. The apparatus according to claim 25, characterized in that, The nanostructure also includes a third dimension having a third dimension parameter of at least about 11 nm and / or a ratio between the third dimension parameter and the first dimension parameter of at least about 10.

69. The apparatus according to claim 68, characterized in that, The third dimension parameter is at least about 1 mm.

70. The apparatus according to claim 68, characterized in that, The ratio between the third dimension parameter and the first dimension parameter is at least about 1,000.

71. The apparatus according to claim 69 or 70, characterized in that, The third dimension parameter is at least about 1 mm, and the ratio between the third dimension parameter and the first dimension parameter is at least about 1,000.

72. The apparatus according to claim 69, characterized in that, The second dimension parameter is at least about 1 mm.

73. The apparatus according to claim 69, characterized in that, The ratio between the second dimension parameter and the first dimension parameter is at least about 1,000.

74. The apparatus according to claim 72 or 73, characterized in that, The second dimension parameter is at least about 1 mm and the ratio between the second dimension parameter and the first dimension parameter is at least about 1,000.

75. The apparatus according to claim 25, characterized in that, The nanostructure is configured as a 2D nanostructure.

76. The apparatus according to claim 68, characterized in that, The nanostructure is configured as a nanosheet.

77. The apparatus according to claim 76, characterized in that, The second dimensional parameter of the nanosheet is at least about 1 mm, 1 cm, 1 m or 10 m.

78. The apparatus according to claim 76, characterized in that, The third dimension parameter of the nanosheet is at least about 1 mm, 1 cm, 1 m or 10 m.

79. The apparatus according to claim 77 or 78, characterized in that, The second dimension parameter and the third dimension parameter of the nanosheet are at least about 1 cm, 1 m or 10 m.

80. The apparatus according to claim 75, characterized in that, The core of the 2D nanostructure includes carbon atoms or metal atoms.

81. The apparatus according to claim 25, characterized in that, The core of the nanostructure is prepared by a top-down or bottom-up process.

82. The apparatus according to claim 25, characterized in that, The core of the nanostructure is prepared by a method selected from the following: photolithography, electrophoresis, suspension, electrochemical deposition, vapor deposition, vapor-liquid-solid (VLS), ion trajectory, melt processing, interfacial polymerization, electrospinning, solvent-resistant polymer precipitation, catalytic synthesis, liquid-phase synthesis, and "island in the sea".

83. The apparatus according to claim 25, characterized in that, The nanostructure is prepared by combining the core and the outer surface to form the nanostructure.

84. The apparatus according to claim 83, characterized in that, The core and the outer surface combine to form the nanostructure in the presence of external energy at the junction.

85. The apparatus according to claim 84, characterized in that, The external energy source is mechanical energy, acoustic energy, or thermal energy.

86. The apparatus of claim 24, comprising a plurality of nanostructures forming a nanostructure network.

87. The apparatus according to claim 86, characterized in that, The nanostructure network includes multiple nanostructures as components of claim 24.

88. The apparatus according to claim 86, characterized in that, The nanostructure network comprises at least two nanostructures as described in claim 24.

89. The device of claim 87, comprising a multilayer nanostructure network to form a nanoscaffold.

90. The apparatus according to claim 89, characterized in that, The nanoscaffold comprises at least one layer of the nanostructure.

91. The apparatus according to claim 1, characterized in that, The box or adsorbent includes a complete surface containing the cell membrane.

92. The apparatus according to claim 1, characterized in that, The box or adsorbent comprises at least two of the following: 1) Nanoparticles containing cell membranes; 2) Nanostructures containing cell membranes; 3) An intact surface containing the cell membrane.

93. The apparatus according to claim 1, characterized in that, The cell membrane is derived from blood cells, tumor cells, cancer cells, immune cells, stem cells, endothelial cells, neurons, exosomes, secretory vesicles, and / or synaptic vesicles.

94. The apparatus according to claim 93, characterized in that, The cell membrane is derived from erythrocytes, platelets, macrophages, neutrophils, and / or neurons.

95. The apparatus according to claim 93, characterized in that, The cell membrane originates from macrophages.

96. The apparatus according to claim 93, characterized in that, The cell membrane is derived from macrophages and neutrophils.

97. The apparatus according to claim 93, characterized in that, The cell membrane is derived from red blood cells and platelets.

98. The apparatus according to claim 93, characterized in that, The cell membrane is derived from red blood cells, platelets, and neurons.

99. The device according to claim 1, having a length ranging from 0.01m to 1m.

100. The apparatus according to claim 1, comprising: (square meters) to approximately The cross-sectional surface area within the range of (square meters).

101. The device according to claim 1 is an extracorporeal blood purification (EBP) device.

102. The apparatus according to claim 1, characterized in that, The cell membrane originates from different types of cells.

103. A device assembly comprising at least two devices of claim 1, wherein the at least two devices are in fluid communication and include a housing or adsorbent, the housing or adsorbent comprising cell membranes derived from different types of cells.

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