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48 results about "Antigen delivery" patented technology

Oral vaccine containing largemouth bass iridovirus ATPase as well as preparation method and application of oral vaccine

A spore of a bacillus subtilis B.subtilis WB600 strain is used as an antigen delivery carrier, spore coat protein C (CotC) is used as anchoring protein, a key protein ATPase gene and a CotC gene of micropterus salmoides iridovirus are fused through a gene fusion technology, a recombinant spore surface display system is constructed, the ATPase antigen is stably displayed on the spore surface, and an oral vaccine is prepared. After being orally applied to fishes, the vaccine can tolerate the gastrointestinal tract environment and is accurately delivered to intestinal related lymphatic tissues to stimulate fish immunity, and finally prevention and control of the iridovirus of the micropterus salmoides are achieved.
Owner:JIMEI UNIV

Cationic manganese nano adjuvant as well as preparation method and application thereof

The invention relates to a cationized manganese nano adjuvant as well as a preparation method and application thereof. The cationized manganese nano adjuvant comprises manganous-manganic oxide nano particles and cationized template molecules wrapping the surfaces of the manganous-manganic oxide nano particles, the cationization template molecule is a protein subjected to cationization modification treatment, or a protein fragment thereof, or a polypeptide fragment thereof. Precise regulation and control of surface charges and structures of the manganese nanoparticles are realized through a biomineralization technology, and the key problems of a traditional vaccine adjuvant in the aspects of antigen delivery, immune activation and biocompatibility are effectively solved. The cationized manganese nano adjuvant can efficiently adsorb various antigens to form a stable nano vaccine compound, and congenital immunity and adaptive immunity response of an organism can be remarkably activated; lymph nodes can be effectively targeted, the enrichment degree of antigens in the lymph nodes is improved, and the immune effect is further enhanced; meanwhile, the biotoxicity is low, and the stability is excellent.
Owner:THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA

Allosteric nanogel adjuvant as well as preparation method and application thereof

The invention provides an allosteric nanogel adjuvant as well as a preparation method and application thereof, and belongs to the technical field of vaccines. The allosteric nanogel adjuvant comprises a self-assembly motif, a responsive site and an immunomodulatory peptide fragment, and the self-assembly motif is composed of 2-5 amino acids; the allosteric nanogel adjuvant has a structure as shown in a formula I, and is named as NTP5 for short; the allosteric nanogel adjuvant is self-assembled into nanoparticles, the nanoparticles are allosteric into a nanofiber structure through responsive broken bonds, nanogel is further formed, and the key problems of a traditional vaccine in the aspects of antigen delivery and immune activation are effectively solved. The nanogel adjuvant can efficiently load various antigens to form a stable nano vaccine, activate an immune microenvironment and provide more means and thoughts for vaccine development.
Owner:LIAOCHENG UNIV

Viral vectors for expression of synthetic cancer antigens and chemokine and related methods and uses

PCT designated stageWO2026117753A1Polypeptide with localisation/targeting motifChemokinesAntigen deliveryCancer antigen
The present disclosure generally relates to a viral vector carrying a synthetic cancer antigen and a chemokine. Also provided herein are compositions and uses of the viral vector for delivering, such as tagging, a tumor with the synthetic cancer antigen.
Owner:DISPATCH BIOTHERAPEUTICS INC +1

Preparation method and application of lipid nanoparticles based on phenolic hydroxyl lipids for peptide antigen / manganese adjuvant co-delivery.

PendingCN122297655APeptide antigenEfficacy
This invention discloses a lipid nanoparticle co-delivery system based on phenolic hydroxyl lipids and a manganese adjuvant. Addressing the shortcomings of traditional HPV therapeutic peptide vaccines—weak immunogenicity, easy degradation and inactivation in vivo, low bioavailability of manganese ion adjuvants making spatiotemporal co-delivery with antigens, and poor encapsulation efficiency and insufficient biosafety of conventional lipid nanocarriers—this invention constructs an integrated nanovaccine delivery system by embedding phenolic hydroxyl functional lipids into a nanocarrier framework, synergistically loading HPV E6 / E7 specific antigen peptides and manganese ion immune adjuvants. This system achieves efficient delivery, immune activation, and anti-tumor efficacy, integrating the functions of efficient antigen delivery, potent immune activation, and precise anti-tumor action. The preparation process is simple and exhibits excellent stability, overcoming the limitations of traditional HPV peptide vaccines with poor efficacy when used alone. It has broad research value and clinical translation prospects in the field of precision immunotherapy for HPV-related cervical cancer, head and neck squamous cell carcinoma, and other malignant tumors.
Owner:HENAN UNIVERSITY

Improved adenoviral vectors for antigen delivery

PCT designated stageWO2025240698A1Viral antigen ingredientsVirus peptidesAntigen deliveryNucleotide
A modified adenoviral vector, lacking splice acceptor dinucleotides in a region of the vector and having improved expression is provided.
Owner:VAXART INC

Conjugates for antigen delivery and uses thereof

The present invention relates to a conjugate comprising an mRNA of an antigen protein and an mRNA encoding a carrier protein linked to the 5'terminal and the 3 'terminal of the mRNA of the antigen protein, and an vaccination composition and / or a vaccine composition comprising the conjugate, the present invention having an effect of stably increasing the expression of an antigen protein.
Owner:LG CHEM LTD

An oral nano-medicine antigen delivery system, its construction method and application

ActiveCN122057037BTumor responseTumor antigen
This invention relates to an oral nanomedicine antigen delivery system and its construction method and application, belonging to the field of oral nanomaterials technology; the construction method includes the following steps: (1) preparation of OM nanoparticle suspension; (2) preparation of cationic liposome suspension; (3) preparation of cationic liposome suspension loaded with OM / BF; (4) construction of oral nanomedicine antigen delivery system. This invention breaks through multiple barriers in the gastrointestinal tract, improves drug bioavailability, and achieves precise immune tracking through the OVA tumor antigen model, simulating in vivo anti-tumor CTL response, thereby exerting anti-tumor effects synergistically at the cellular, tissue, and immune levels, effectively solving the problems of poor water solubility and low delivery efficiency of the active ingredient bufotoxin in traditional Chinese medicine. At the same time, through macrophage-mediated immune regulation and precise drug release, it improves targeting and treatment efficiency, opening up a new avenue for tumor immunotherapy with oral nanomedicine.
Owner:BINZHOU MEDICAL COLLEGE

HIV envelope protein chimeric exosome and preparation method and application thereof

The application discloses a kind of based on HIV envelope protein chimeric exosome and its preparation method and application, belong to biological medicine technical field.The application first constructs the cell line of stable expression HIV envelope protein Env, obtains engineered exosome from cell culture supernatant separation and purification;The exosome is used as immunogen combined with adjuvant immunization experimental animal, and high-efficiency induction specific humoral immune response;Again, obtain Env antigen specificity single B cell by flow cytometry sorting, obtain antibody variable region gene by single cell lysis, reverse transcription and nest PCR amplification, cloning to expression vector and expressing in mammalian cell, finally, HIV specific neutralizing antibody is screened by binding activity, affinity and neutralizing activity;The application is combined with single B cell antibody screening technology by embedding HIV Env antigen in the form of membrane combination in exosome surface, and realizes the synergistic optimization of antigen delivery and antibody screening process.
Owner:WUHAN UNIV OF SCI & TECH

Functional nanomaterials based on choline phosphate-cell membrane interaction and applications thereof

The present application relates to the technical field of medicine, in particular to a functional nanomaterial based on choline phosphate-cell membrane interaction and application thereof.The present application modifies manganese mineralized black phosphorus nanomaterial by bio-inspired polymer pGluCP adsorption, which retains the excellent biocompatibility and photothermal performance of BP, and at the same time, pGluCP enhances the 'chassis' effect of the material, captures tumor-related antigens, and can simultaneously capture water-soluble antigens and water-insoluble membrane antigens and form pathogen-like micro-nanoparticles, which is helpful for antigen delivery and APC presentation, and provides a feasible tool for capturing non-water-soluble membrane antigens, which is a major challenge.MnBP and pGluCP synergistically act, and can realize the personalized conversion of autologous tumors to vaccine production and delivery.
Owner:THE FIRST AFFILIATED HOSPITAL OF GUANGZHOU MEDICAL UNIV (GUANGZHOU RESPIRATORY CENT)

FcRn-targeted Brucella multi-epitope nano vaccine as well as preparation method and application thereof

The invention provides an FcRn-targeted Brucella multi-epitope nano vaccine, which can realize long-term protection, shows continuous immune memory, has high-frequency hair-growing central B cells (GCB), follicular helper T cells (TFH) and central memory T cells (TCM), and ensures long-term immune surveillance; even six months after immunization, the serum IgG titer is still obviously higher than that of a control group; efficient antigen delivery can be achieved, specifically, a chitosan-based nano-particle system is adopted, and antigen protection and intestinal epithelium uptake are enhanced through FcRn targeted ligand modification; the delivery efficiency can be improved by 10 times, and the gastrointestinal mucosal barrier is overcome; in addition, rapid immune starting can be achieved, multi-dimensional immune response is induced within 14 days after final immunization, and rapid protection is provided for resisting brucella infection.
Owner:新疆医科大学第四附属医院

An engineered potent dendritic cell vaccine and preparation method and application thereof

ActiveCN120381516BReduce immune toleranceImprove anti-tumor immune responseCancer antigen ingredientsPharmaceutical non-active ingredientsLysosomePartial antigen
The application discloses an engineered potent dendritic cell vaccine and a preparation method and application thereof, and utilizes a nano-scale antigen delivery mode to fuse tumor antigens with cationic liposomes, destroys the stability of a lysosome membrane by means of cationic liposome charge interaction, makes part of the antigens escape into a cytoplasm to be cross-presented through an MHC I pathway, gives the DCs the ability to activate a cellular immune response to resist tumors, on the other hand, gives the DCs T cell directivity through a synthetic immunology method, promotes the interaction and signal transmission of DC-T cells, and the combination of the two mechanisms can overcome the low response rate problem of the existing DC vaccine, and maximizes the anti-tumor immune response.
Owner:THE AFFILIATED HOSPITAL OF QINGDAO UNIV

Recombinant fusion protein for antigen delivery and uses thereof

The present invention relates to a fusion protein comprising a peptide antigen containing a T cell epitope, a first carrier protein linked to the N-terminus of the peptide antigen, and a second carrier protein linked to the C-terminus of the peptide antigen; a nucleic acid molecule encoding the fusion protein; an expression vector containing the nucleic acid molecule; a cell transformed with the expression vector; and an immunogenic composition comprising the fusion protein, the nucleic acid molecule, the expression vector, or the cell.
Owner:LG CHEM LTD

Peptide vaccine compositions and pharmaceutical preparations for reducing the progression of atherosclerosis

A peptide vaccine composition for reducing the progression of atherosclerosis comprises peptides derived from the E3 region of the TRPM2 ion channel from various species, either alone or in combination. A pharmaceutical formulation comprises the peptide vaccine composition and an adjuvant. By utilizing the TRPM2 peptides, the peptide vaccine composition and pharmaceutical formulation of the present invention are capable of producing effective anti-TRPM2 polyclonal antibodies that can reduce the progression of atherosclerosis in an apoE knockout mouse model. Furthermore, the present invention identifies the most suitable antigen delivery pathway for endogenously producing anti-TRPM2 polyclonal antibodies to alleviate atherosclerosis.
Owner:THE CHINESE UNIVERSITY OF HONG KONG

Responsive antigen-capturing nano-platform, and preparation method and application thereof

The present application relates to the technical field of tumor immunotherapy. The present application provides a responsive antigen capture nano platform, a preparation method and application thereof. The product of the present application is applied by systemic administration such as intravenous injection; can specifically respond to peroxynitrite in the tumor microenvironment, realize the precise activation of the tumor site; can covalently capture tumor-related antigens through high efficiency, deliver the antigens to antigen presenting cells, so as to enhance the anti-tumor immune response; combined with photodynamic therapy can significantly inhibit tumor growth.
Owner:NANKAI UNIV

Core domains of annexin and their use in antigen delivery and vaccination

The present disclosure provides immunogenic compositions, such as vaccines, including DNA vaccines, and uses thereof, for example, including annexin core domains for mediating effective antigen delivery and antigen presentation to induce antigen-specific immune responses, and / or to treat or prevent infectious diseases and / or cancer.
Owner:DEUTES KREBSFORSCHUNGSZENT STIFTUNG DES OFFENTLICHEN RECHTS

Oral nano traditional Chinese medicine antigen delivery system as well as construction method and application thereof

The invention relates to an oral nano traditional Chinese medicine antigen delivery system as well as a construction method and application thereof, and belongs to the technical field of oral nano materials. The construction method comprises the following steps: (1) preparing an OM nanoparticle suspension; (2) preparing a cationic liposome suspension; (3) preparing an OM / BF loaded cationic liposome suspension; and (4) constructing an oral nano traditional Chinese medicine antigen delivery system. According to the invention, multiple barriers of gastrointestinal tracts are broken through, the bioavailability of drugs is improved, precise immune tracking is realized through an OVA tumor antigen model, and in-vivo anti-tumor CTL reaction is simulated, so that an anti-tumor effect is synergistically exerted on three levels of a cell level, a tissue level and an immune level; according to the preparation method, the problems of poor water solubility and low delivery efficiency of bufalin serving as a traditional Chinese medicine active ingredient are effectively solved, meanwhile, through macrophage-mediated immunoregulation and accurate drug release, the targeting property and the treatment efficiency are improved, and a new way is opened up for tumor immunotherapy of oral nano traditional Chinese medicines.
Owner:BINZHOU MEDICAL COLLEGE

Langerhans cells targeting HIV-1 vaccines

PCT designated stageWO2025202674A1Antibody mimetics/scaffoldsViral antigen ingredientsLangerhan cellDendritic cell
Developing an effective HIV-1 vaccine is contingent on generating protective antibodies (Abs). Novel antigen delivery methods are needed to enhance immune responses. One promising approach involves directing antigens to dendritic cells (DC) through fused monoclonal antibodies (mAbs) to amplify both cellular and humoral responses. Here, the inventors aimed to refine Langerhans cells (EC) targeting by designing three Env monochains instead of 2 (EC3. Env3) mimicking natural Env conformation. The inventors demonstrated that EC3. Env3 construct (i) elicited a rapid and potent Env-IgG response, (ii) enhanced the avidity of anti-Env IgG that was accompanied by a marked expansion of Tfh and GC B cells and (iii) swiftly induced the formation of structured germinal centers in dLN, indicative of a robust immune response. Finally, significant Tier-1 NeutAb induction was observed in rabbits immunized with the construct. In conclusion, HIV Env antigen can be adaptively targeted to LC as a timer, intensifying both the magnitude and quality of humoral responses. The present invention thus relates to the use of such a construct as LC targeting HIV-1 vaccines.
Owner:INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +2

Compositions, kits, methods, and methods of administration relating to edwardsiella piscicida vaccine and / or antigen delivery vector systems

In one aspect, the disclosure relates to recombinant bacterial vectors including a gene encoding at least one antigen from Aeromonas hydrophila or tilapia lake virus, methods of making the same, vaccines incorporating the same, and methods of inducing an immune response in the subject and / or preventing infection by a pathogen in the subject using the same. In one aspect, the subject is a fish in an aquaculture system. In an aspect, the vector or vaccine can be administered by bath immersion or intracoelomic injection and, in some cases, can confer protection against an additional pathogen such as, for example, Edwardsiella piscicida. In any of these aspects, the vectors are susceptible to antibiotics and do not persist in the environment.
Owner:UNIV OF FLORIDA RESEARCH FOUNDATION INC

Microbial carrier vaccine, preparation method thereof and vaccine composition

The invention provides a microbial carrier vaccine, a preparation method thereof and a vaccine composition. A microbial carrier vaccine for antigen delivery with an enteric microbial delivery system is provided, and the enteric microbial delivery system is selected from at least one of a bacteriophage delivery system (e.g., Klebsiella pneumoniae bacteriophage), an Escherichia coli delivery system (e.g., Klebsiella pneumoniae bacteriophage), and an antigen delivery system (e.g., Klebsiella pneumoniae bacteriophage). Escherichia coli S17-1 lambda pi) or a conjugation delivery system of Escherichia coli and intestinal symbiotic bacteria. The microbial carrier vaccine is a vaccine platform developed based on intestinal microorganisms, after the vaccine enters a body, intestinal symbiotic bacteria can be subjected to in-situ editing, so that the intestinal symbiotic bacteria can continuously generate antigens to be applied to the body, the body can be continuously stimulated to generate antibodies, and the continuous protection effect is achieved.
Owner:SHENZHEN HUADA GENE INST

Application of nano-selenium biological particle as protein vaccine carrier or preparation of antibacterial infection medicine or antioxidant medicine

The invention discloses an application of nano-selenium biological particles as a protein vaccine carrier or preparation of an antibacterial infection drug or an antioxidant drug, and belongs to the technical field of vaccine delivery carriers. The invention aims to provide a novel microbial particle which is used as an anti-infection and anti-oxidation drug, can induce training immunity, and has multiple functions of antibiosis, anti-infection, anti-oxidation and antigen delivery. The invention provides an application of a nano-selenium biological particle as a protein vaccine carrier, or preparation of a bacterial-like particle for preventing bacterial infection, or an application of the nano-selenium biological particle as an antioxidant drug. In-vitro RAW264.7 cells and in-vivo mouse peritoneal macrophages are induced to generate a training immunophenotype, and the vaccine can be used as a vaccine delivery vector to be connected with a staphylococcus aureus mode antigen to design a novel multifunctional biological material by utilizing training immunity to resist multi-drug-resistant bacterium infection, which is a novel strategy.
Owner:NORTHEAST AGRICULTURAL UNIVERSITY

Recombinant fusion protein for antigen delivery and uses thereof

The present invention relates to a fusion protein comprising a peptide antigen containing a T cell epitope, a first carrier protein linked to the N-terminus of the peptide antigen, and a second carrier protein linked to the C-terminus of the peptide antigen; a nucleic acid molecule encoding the fusion protein; an expression vector containing the nucleic acid molecule; a cell transformed with the expression vector; and an immunogenic composition comprising the fusion protein, the nucleic acid molecule, the expression vector, or the cell.
Owner:LG CHEM LTD

Preparation method and application of vesicle vaccine based on chitosan antigen delivery system

The invention discloses a preparation method and application of a vesicle vaccine based on a chitosan antigen delivery system, the vesicle vaccine stimulates cells to secrete the vesicle vaccine with an antigen presentation function, and the method related to the system specifically comprises the following steps: step 1, mixing antigen protein with a chitosan aqueous solution and a sodium tripolyphosphate aqueous solution, and carrying out electrostatic interaction to obtain a vesicle vaccine solution; chitosan nanoparticles loaded with the antigen protein are prepared; and 2, treating immune cells by using the antigen-loaded chitosan nanoparticles, collecting cell culture supernatant, and collecting and preparing vesicles by adopting a method of combining multi-step differential centrifugation with ultrafiltration. After the antigen delivery system based on chitosan is co-incubated with cells, antigen protein can be effectively delivered into immune cells, meanwhile, the immune cells are promoted to generate a large number of antigen-related vesicles with efficient immunogenicity through the adjuvant effect and autophagy regulation effect of chitosan, and the immunogenicity of the antigen-related vesicles is improved. The application potential of the artificial antigen presenting cell is realized.
Owner:LIANGZHU LAB

Chimeric virus-like particle vaccine against rotavirus

The present disclosure relates to a recombinant chimeric virus-like particle (cVLP) vaccine composition against rotavirus infection. The vaccine comprises a virus-like particle fragment including a hepatitis B core (HBc) protein functioning as an adjuvant, into which a heterologous immunogenic domain derived from the rotavirus VPS* protein is inserted within the major immunodominant region (MIR) of HBc. The construct is encoded by SEQ ID NO. 1, and expressed in a prokaryotic system. The cVLPVPS* vaccine composition of the present disclosure offers a non-replicating, protein-based alternative to live attenuated vaccines, and the platform may help address challenges related to safety, strain specificity, and antigen delivery.
Owner:SHOJA ZABIHOLLAH +7

Optimized tag part

The present disclosure provides improved peptide tag moieties with affinity for binding molecules. The peptide tag moieties are useful, for example, as part of tag constructs, together with cargo moieties. They offer unexpected advantages as part of biopharmaceutical product conjugates compared to known tag moieties with similar amino acid sequences. Also disclosed are binding molecules and bispecific conjugates with affinity for the peptide tag moieties, as well as conjugates comprising a peptide tag moiety non-covalently bound to such binding molecules or bispecific conjugates. In such conjugates, the tag moiety can form part of a tag construct that further comprises an antigen as a cargo moiety, for example, for antigen delivery to immune cells. Medical uses of the tag moieties, tag constructs, and conjugates of the present disclosure are also provided.
Owner:STRIKE PHARM AB

Binding molecules

The present disclosure provides an improved binding molecule comprising an immunoglobulin binding domain having an affinity for a peptide tag moiety. The binding molecules can be used, for example, as part of bispecific conjugates. The binding molecules exhibit unexpected advantages as part of biopharmaceutical products as compared to known binding molecules with similar binding affinity. The disclosure also provides bispecific conjugates comprising a binding molecule and complexes comprising a bispecific conjugate non-covalently bound to a tag construct comprising a peptide tag moiety and a cargo domain comprising an antigen for delivery of the antigen to an immune cell. The disclosure also provides medical uses of the binding molecules, conjugates and complexes of the disclosure.
Owner:STRYKER DRUG CORP

CD40 binding protein, bispecific conjugate thereof and method of treating cancer

Provided is a binding protein that binds CD40 and is an agonist thereof. In a particular embodiment the invention provides an agonistic anti-CD40 antibody. Also provided are bispecific conjugates comprising the binding protein, and complexes comprising the bispecific conjugates non-covalently bound to a tag construct comprising an antigen, for antigen delivery to immune cells. Medical uses of the binding proteins, conjugates and complexes of the invention are also provided.
Owner:STRIKE PHARM AB

A method for the synthesis of spherical polymer nanoparticles

ActiveCN117603417Bgood size controlvariable sizeNanotechnologyAntibody medical ingredientsPyrrolidinonesCross linker
The application discloses a kind of synthesis method of spherical polymer nanoparticles, it is related to vaccine technical field, and the method comprises the following steps: polyvinylpyrrolidone is dissolved in mixed solvent, then glyoxal, ascorbic acid and ethylenediamine are added in turn respectively, after stirring for a certain time, the color of solution obviously changes from yellowish to wine red.The solution containing prepolymer is transferred into reaction kettle, the reaction kettle is put into oven to react, the previous prepolymer will further crosslink and polymerize, form nonlinear network polymer skeleton, through repeated centrifugation and ethanol washing, finally drying can obtain the target spherical nanoparticle material.The application uses ascorbic acid as raw material, ethylenediamine as initiator and connecting agent, glyoxal as crosslinking agent, successfully synthesizes a kind of brand-new polymer nanoparticle, simultaneously realizes efficient antigen delivery and specific activation B cell, and is a kind of brand-new ideal vaccine adjuvant with promising application.
Owner:JILIN UNIVERSITY

Recombinant fusion proteins for antigen delivery with modified cysteine ​​residues and uses thereof

PendingJP2026501641AFungiBacteriaPeptide antigenAntigen delivery
The present invention relates to a fusion protein comprising a peptide antigen and a human thioredoxin protein linked to the N-terminus, C-terminus, or both, of the peptide antigen, wherein all cysteine ​​residues in the amino acid sequence of the human thioredoxin protein have been substituted with non-cysteine ​​residues; a nucleic acid molecule encoding the fusion protein; an expression vector comprising the nucleic acid molecule; a cell transformed with the expression vector; and a composition comprising the fusion protein, nucleic acid molecule, expression vector, or cell.
Owner:LG CHEM LTD

Fluorine-nitrogen modified polymer immunoadjuvant material, preparation method and application thereof

The application discloses a fluorine-nitrogen modified high-molecular immunoadjuvant material, a preparation method and application thereof, and belongs to the technical field of high-molecular materials and immunology, wherein the high-molecular immunoadjuvant material comprises a biodegradable polycarbonate main chain, and polyethylene glycol segments, perfluoroalkyl side chains and nitrogen-containing seven-membered ring side chains connected to the polycarbonate main chain. The perfluoroalkyl side chains are introduced to promote antigen delivery and improve the antigen presenting cell uptake efficiency; the nitrogen-containing seven-membered ring side chains are introduced to the side chains to make the material have intracellular environment response characteristics, so that the antigen intracellular release process is improved and the antigen utilization efficiency is improved. In addition, the polycarbonate which can be completely degraded by enzymes in the body is used as the main chain framework, so that the material has good delivery performance and biological safety.
Owner:JILIN UNIVERSITY