501 results about "Endocytosis" patented technology

A composition comprising intact minicells that contain a drug molecule is useful for targeted drug delivery. One targeted drug delivery method employs bispecific ligands, comprising a first arm that carries specificity for a bacterially derived minicell surface structure and a second arm that carries specificity for a mammalian cell surface receptor, to target drug-loaded minicells to specific mammalian cells and to cause endocytosis of the minicells by the mammalian cells. Another drug delivery method exploits the natural ability of phagocytic mammalian cells to engulf minicells without the use of bispecific ligands.

The present invention provides for the development of endocytosis-sensitive probes, and a remote method for measuring cellular endocytosis. These probes are based on the reduced water permeability of a nanoparticle or liposomal delivery system, and inherent degradability or disruption of barrier integrity upon endocytosis. The invention also provides for liposomes having combined therapeutic and diagnostic utilities by co-encapsulating ionically coupled diagnostic and therapeutic agents, in one embodiment, by a method using anionic chelators to prepare electrochemical gradients for loading of amphipathic therapeutic bases into liposomes already encapsulating an imaging agent. The invention provides for imaging of therapeutic liposomes by inserting a lipopolymer anchored, remotely sensing reporter molecules into liposomal lipid layer. The invention allows for an integrated delivery system capable of imaging molecular fingerprints in diseased tissues, treatment, and treatment monitoring.

A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, or a fragment thereof, which protease or protease fragment is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a dynorphin Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent; a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease or fragment thereof and the dynorphin Targeting Moiety; and a translocation domain that is capable of translocating the protease or protease fragment from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described.

Methods and compositions are provided for delivering a polynucleotide encoding a gene of interest to a target cell using a virus. The virus envelope comprises a cell-specific binding determinant that recognizes and binds to a component on the target cell surface, leading to endocytosis of the virus. A separate fusogenic molecule is also present on the envelope and facilitates delivery of the polynucleotide across the membrane and into the cytosol of the target cell. The methods and related compositions can be used for treating patients having suffering from a wide range of conditions, including infection, such as HIV; cancers, such as non-Hodgkin's lymphoma and breast cancer; and hematological disorders, such as severe combined immunodeficiency.

A method of identifying a combination of antibodies with a combined improved anti tumor activity is provided. The method comprising identifying at least two anti RTK antibodies capable of inducing synergistic endocytosis of the RTK in a cell expressing the RTK, thereby identifying the combination of antibodies with the combined improved anti-tumor activity.

The invention belongs to the medicinal preparation field, relates to a cell-penetrating peptide modified nanoparticle, and concretely relates to a nanoparticle delivery system for oral polypeptide and protein medicines, and its preparation method. The medicine delivery system is composed of the nanoparticle, cell-penetrating peptides modified on the surface of the nanoparticle, and the polypeptide protein medicines sealed by the nanoparticle, wherein the average particle size range of the medicine delivery system is 10-500nm. The cell-penetrating peptide modified nanoparticle and glucosaminoglycan having electronegative cell surfaces undergo electric property attraction and then undergo endocytosis, so the cell-penetrating peptide modified nanoparticle and the glucosaminoglycan are integrally taken into cells; and the cell-penetrating peptide modified nanoparticle has an alimentary canal mucous membrane penetrating capability after the cell-penetrating peptide modified nanoparticle is orally taken, and can deliver the polypeptide protein medicines carried by the cell-penetrating peptide modified nanoparticle to the whole body for blood circulation, so the oral biological utilization degree of the medicines are improved. The cell-penetrating peptide modified nanoparticle has the advantages of improvement of the stability of polypeptide and protein medicines in the alimentary canal, reduction of the application amount of cell-penetrating peptides, and reduction of possible toxic side effects caused by the cell-penetrating peptides.

A fusion protein for delivery of a wide variety of agents to a cell via antibody-receptor-mediated endocytosis comprises a first segment and a second segment: the first segment comprising a variable region of an antibody that recognizes an antigen on the surface of a cell that after binding to the variable region of the antibody undergoes antibody-receptor-mediated endocytosis, and, optionally, further comprises at least one domain of a constant region of an antibody; and the second segment comprising a protein domain selected from the group consisting of avidin, an avidin mutein, a chemically modified avidin derivative, streptavidin, a streptavidin mutein, and a chemically modified streptavidin derivative. Typically, the antigen is a protein. Typically, the protein antigen on the surface of the cell is a receptor such as a transferrin receptor-or an insulin receptor. The invention also includes an antibody construct incorporating the fusion protein that is either a heavy chain or a light chain together with a complementary light chain or heavy chain to form an intact antibody molecule. The invention further includes targeting methods and screening methods.

The invention relates to a multi-function nano prodrug system based on a dendrimer, which belongs to the technical field of biomedicines and nano medical science. The nano system comprises four function parts: an outermost layer RGD (arginyl-glycocoll-aspartate) cyclic peptide as an active targeting head group (1), a polyethylene glycol (PEG) hydrophilic chain segment (2) connected with the targeting head group and the dendrimer, an anti-tumour drug (3) connected with the dendrimer by an acid sensitive chemical bond and a dendrimer kernel (4). The general formula of the nano system is RGD-PEG-Dendrimer-DOX (doxorubicine), wherein the macromolecule attribute of a dendrimer vector makes a vector system passively target to tumor tissues through an EPR (Enhanced Permeability and retention) effect; the RGD cyclic peptide makes the vector system actively target to the tumor tissues through the interaction of a ligand and a receptor and promotes the endocytosis of the tumor tissues; the acid sensitive chemical bond ensures that a drug-carrying system is stable in systemic circulation and releases active drugs after arriving tumor positions and entering an acid organelle to perform the function of cytotoxicity.

The invention provides a novel polypeptide modified tumor targeted liposome of a targeted integrin receptor. The novel polypeptide is mainly formed by covalent linkage of ring-shaped RGD and cell penetrating peptides, and not only has the selective targeting capability of an integrin receptor, but also can achieve mediated endocytosis; the liposome mainly comprises phospholipid, cholesterol, lipid-polyethyleneglycol and lipid-polyethyleneglycol-novel polypeptide ligand chimeric substance, and is a very potential tumor targeted treatment carrier.

The invention discloses an exosome-encapsulated nano drug-loading system for tumor treatment, and preparation thereof. The system is obtained by utilizing cell endocytosis of a drug-loading nanometermaterial and then exocytosis. The drug-loading nanometer material is loaded with an antitumor medicine including at least one of a chemotherapeutic, a medicine used for immunotherapy and a medicine used for modifying a tumor microenvironment. The composition, structure and the like of the key outer component biofilm encapsulating the nano drug-loading system are improved, and compared with the prior art, the exosome-encapsulated nano drug-loading system provides a novel route for biofilm-based biological processed nanoparticles. By utilization of the exosome-encapsulated nano drug-loading system, the composition and the structure of the exosome can be maintained greatly, and the obtained exosome-encapsulated nano drug-loading system has good stability and tumor targeting performance duringblood circulation. .

A method of treating tumor tissue of an individual is provided. The method is effected by applying to cells of the tumor tissue electrical field pulses having a strength, a repetition frequency and a pulse width selected capable of inducing endocytosis mediated cell death thereby treating the tumor tissue.

A biodegradable cationic polymer is disclosed. The biodegradable cationic polymer of the invention has amino groups in the backbone and side chains, self-assembles cationic complexes with nucleic acids, and delivers nucleic acids into a cell by endocytosis. The biodegradable cationic polymer of the invention also has very low cytotoxicity. Methods of making and using the biodegradable cationic polymer are further disclosed.

The invention discloses a glutathione-modified chitosan copolymer serving as a non-viral gene carrier material and preparation and application thereof, which belong to the fields of gene therapy and novel materials. A preparation method of the copolymer comprises the following steps of: (1) synthesizing an allyl-modified chitosan derivative; (2) synthesizing brush-like PEG (Polyethylene Glycol) polymer chains with different molecular weights through RAFT (Reversible Addition-Fragmentation Chain Transfer); (3) grafting the brush-like PEG onto a chitosan framework by adopting a free radical coupling method; and (4) linking glutathione to the chain end of the brush-like PEG by adopting an EDC (1-Ethyl-3-(3-Dimethyllaminopropyl) Carbodiimide hydrochloride)/NHS (N-hydroxysuccinimide) activation method to obtain a glutathione-modified chitosan copolymer carrier material. The glutathione-modified chitosan copolymer obtained by adopting the technology serves as the non-viral gene carrier material. By adopting the copolymer, the endocytosis function of a composite nanoparticle formed from the copolymer and DNA (Deoxyribonucleic Acid) can be remarkably enhanced, the releasing mechanism of DNA from a composite particle after cell entrance is improved, and the non-viral gene carrier material with a high transfection efficiency is further obtained.

The invention belongs to the field of biotechnology, and relates to a slightly acidic environment targeted polypeptide modified tumor targeted nano drug delivery system, and a preparation method thereof. The slightly acidic environment targeted polypeptide modified tumor targeted nano drug delivery system is prepared via self-assembly of a slightly acidic environment targeted polypeptide modified dendrimer encapsulated gene, wherein the surface of the dendrimer is rich of amino groups. According to the preparation method, a polypeptide of transmembrane helix protein C derived from bacteria visual purple is used for modifying a high molecular carrier, enrichment and adhesion onto cells is realized via a pH sensitive cell membrane insertion method, and entering into cells is realized via electrostatic adsorption guided endocytosis, so that untaking of tumor cells on drugs is improved, and toxic and side effects are reduced. According to the tumor targeted nano drug delivery system, cell membrane is taken as the target point, and the polypeptide is taken as the target head group in tumor slightly acidic environment, targeting and curing efficiency are high, the preparation method is simple and convenient, and tumor cell drugs, which are derived from human or animal, and is used for targeted therapy, can be prepared.

The invention discloses functional albumin and a preparation method of a nano preparation of the functional albumin. The nano preparation of the functional albumin consists of the functional albumin, metal ions and a drug; the metal ions can simultaneously form coordination bonds with the functional albumin and the drug, and can form nanoparticles through induced self-assembly. The nano preparation, through an endocytosis mediated by an albumin receptor (SPARC) on the surface of tumor cells, can deliver the drug into the drug-resistant tumor cells, so as to effectively avoid the exocytosis effect of a p-gp pump on the drug, and then as the coordination bonds break in an acid tumor cell environment through a pH responsibility, the drug releases in cytoplast, enters cell nucleus and inlays in DNA so as to inhibit the synthesis of nucleic acid; and therefore, the growth of the tumor cells is inhibited. Through in vitro characterization, the nano preparation can achieve the relatively good pH responsibility; and through activity evaluation on a cellular level, the system is capable of effectively delivering the drug into the cells, so as to achieve relatively good pH responsive release.

The invention discloses an interface-cross-linked temperature-sensitive polymer vesicle and a method for preparing the same. The interface-cross-linked temperature-sensitive polymer vesicle is formed by a block copolymer which at least comprises a hydrophilic block, a cross-lined interstrand block and a temperature sensitive block, wherein the hydrophilic block forms the membrane shell of the polymer vesicle, the temperature sensitive block forms the membrane nuclear of the polymer vesicle, and the cross-lined interstrand block forms the interface of the polymer vesicle to cross-link the interface of the polymer vesicle to stabilize the structure of the vesicle, and thus the interface-cross-linked temperature-sensitive polymer vesicle is formed; as the vesicle is formed in an aqueous solution system and the interface of vesicle is cross-linked, the small molecule drug, macromolecular drug and probe molecule entrapment efficiency of the polymer vesicle, the circulation stability in vivo blood and the efficiency of endocytosis by tumor cells are improved; and as a result, the bioavailability of drugs is improved and the polymer vesicle can be expelled out of the body conveniently.

The invention discloses an antibody coupling drug targeting on EGFR, a preparation method thereof and uses thereof. The antibody-conjugated drug targeting EGFR is named LR004-VC-MMAE consisting of anantibody, a cytotoxic drug and a linker, wherein the antibody drug conjugate has a structure represented by the formula I, wherein mAb is an LR004 monoclonal antibody, n=2-8. The novel antibody-conjugated drug LR004-VC-MMAE can not only target EGFR antigen, but also has strong cytotoxicity to tumor cells. Compared with LR004 itself, it did not affect the affinity, endocytosis and targeting of theantibody, and better retained its biological function. Compared to LR004, the antitumor effect of LR004-VC-MMAE antibody-conjugated drug is significantly improved, and the tumor disappeared. Comparedto LR004, LR004-VC-MMAE antibody-conjugated total antibody showed longer half-life, slower clearance rate, lower concentration of free MMAE in plasma, shorter half-life and faster clearance rate, which is conducive to reduce toxicity.

The invention discloses an acid sensitive polymer prodrug, nanoparticles of the prodrug and application of the nanoparticles. In the acid sensitive polymer prodrug, a polymer precursor is a vinyl ether-functionalized water-soluble A-B type two-block polymer; drug molecules are linked with the A-B type two-block polymer through an acetal bond; the acid sensitive polymer prodrug is self-assembled in water solution to form predrug micellar nanoparticles in which a polyethylene glycol hydrophilic chain segment serves as an outer surface and an anti-cancer drug bound to a polymer main chain through the acetal bond serves as a hydrophobic core. The pH sensitive prodrug and the nanoparticles of he prodrug are simple in preparation method, and good in tumor inhibitory effect; the nanoparticles also can efficiently encapsulate another hydrophobic anticancer drug; the kill capability to the cancer cell is enhanced; and the efficiency of endocytosis of the cell to the nanoparticles can be enhanced by coupling specific target molecules onto the surfaces of the nanoparticles. Thus, the inhibitory effect on the tumor cell is enhanced.

The invention belongs to the field of chemistry and relates to an organic near-infrared two-photon fluorescent dye with a structure in a formula I in the specification. The organic near-infrared two-photon fluorescent dye has the beneficial effects that after being excited, the organic near-infrared two-photon fluorescent dye simultaneously shows stronger luminous efficiency of single-photon near-infrared fluorescence and two-photon fluorescence; the efficiency of two-photon fluorescence is obviously improved compared with that of other carbocyanine dyes; living cell fluorescence microscope experiments show that probes prepared from the fluorescent dye can enter tumor cell lysosome through endocytosis and can be imaged and simultaneously monitored by single-photon fluorescence and two-photon fluorescence microscopes; the dye can achieve synchronous single-photon near-infrared fluorescence and two-photon fluorescence imaging in the in-vivo and in-vitro states; and the fluorescent dye has the characteristics o good water solubility and stable chemical properties, can be used or bio-macromolecular markers and in the field of medical image diagnosis and especially has strong application value in optical image guided tumor excision.