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Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin Li Qianfeng Zhang Zhiqian Li Long Ren Dayi Pan Qiyong Gong Zhongwei Gu Hao Cai Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their *** address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor *** this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into *** internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP ***,diABZI effectively activated the STING *** with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy

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glycopolymer N-halamine-modified biochars with high specificity for Escherichia coli eradication

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Chinese Journal of Chemical Engineering 2021年第10期34卷 229-236页

作者： Qinggele Borjihan Quanfu Yao Huihui Qu Haixia Wu Ying Liu Alideertu Dong College of Chemistry and Chemical Engineering Inner Mongolia UniversityHohhot 010021China Engineering Research Center of Dairy Quality and Safety Control Technology Ministry of EducationInner Mongolia UniversityHohhot 010021China College of Life and Environmental Sciences Minzu University of ChinaBeijing 100081China College of Chemistry and Environment Hohhot Minzu CollegeHohhot 010051China

Antibiotic-resistant bacteria contamination in environments imposes great threats to human life *** research aims to develop novel targeted antibacterial biochars for achieving high selectivity to kill pathogenic Escherichia coli(***).The glycopolymer N-halamine-modified biochars(i.e.,BCPMA-Cl)were synthesized by the modification of biochars with poly[2-(methacrylamido)glucopyranose-coacrylamide](P(MAG-co-AM),followed by chlorination *** on the results of FTIR,turbidity,XPS,and UV–vis,BCPMA-Cl was successfully synthesized and demonstrated to be able to eliminate Staphylococcus aureus(***)and ***,BCPMA-Cl possessed extremely potent to specific-killing 10^(4) CFU·ml^(-1) of *** with lower hemolytic activity(<5%).Additionally,the antibacterial mechanisms of BCPMA-Cl against bacteria were contact-killing and release-killing contributed by active chlorine(i.e.,Cl^(+)).Therefore,this work provided a cost-effective and facile approach for preparation of functional biochars used for bacteria-specific therapeutic applications via livestock pollutants as well as showing a promising strategy to avoid bacterial resistance.

关键词： Biochars N-halamine glycopolymer Antibacterial coating Specific killing

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MORPHOLOGICAL TRANSITION BETWEEN VESICLES AND TUBULES FOR A glycopolymer-CONTAINING AMPHIPHILIC DIBLOCK COPOLYMER IN AQUEOUS SOLUTIONS

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Chinese Journal of Polymer Science 2001年第3期19卷 297-301页

作者： Zi-chen Li Yue Shen Yu-zeng Liang Fu-mian Li Department of Polymer Science & Engineering College of Chemistry Peking University Beijing 100871, China 北京大学北京

The morphological transition of molecular assemblies in aqueous solutions for a new amphiphilic diblock copolymer induced by changing the initial solvent conditions was studied by transmission electron microscopy (TEM). The copolymer was polystyrene(77)-b-poly[2-(beta -D-glucopyranosyloxy)ethyl acrylate (6)] (PSt(77)-b-PGEA(6)) and the solvent was a mixture of DMF and THF. PSt(77)-b-PGEA(6) yields vesicles and tubules when it is initially dissolved in THF and DMF respectively. The morphological transition between vesicles and tubules can be achieved by simply varying the amounts of THF and DMF, or changing the temperature at which the aggregates were prepared.

关键词： block copolymer amphiphile glycopolymer self-assembly tubule vesicle

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Synthesis of Thermoresponsive Poly( diethyleneglycol methacrylate-co-6-Ovinyladipoyl-D-glucopyranose) glycopolymer via RAFT Polymerization

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Journal of Donghua University(English Edition) 2014年第4期31卷 515-519页

作者：孙衎徐慕儒 SYEDA Um-i-Zahra 聂华丽权静朱利民 College of Chemistry Chemical Engineering and BiotechnologyDonghua University

The monomer 6-O-vinyladipoyl-D-glucopyranose( VAG)was synthesized by lipase catalyzed trans-esterification of divinyladipate with D-glucopyranose. A novel double hydrophilic glycopolymer poly( diethyleneglycol methacrylate-co-6-Ovinyladipoyl-D-glucopyranose)( P( DEGMA-co-VAG)) with narrow polydispersity( PDI) and thermosensitivity was prepared by reversible addition-fragmentation chain transfer( RAFT)polymerization. P( DEGMA-co-VAG) was characterized by1 H NMR,FTIR and gel permeation chromatography( GPC). The characterization of UV-visible spectroscopy showed that the micelles from glycopolymer P( DEGMA-co-VAG) were thermo-responsive and the low critical solution temperature( LCST) could be controlled by the molar ratio of monomers. When the molar ratio of DEGMA and VAG was 2∶ 1,the LCST of P( DEGMA-co-VAG) was36 ℃ in aqueous solution,which could form nano micelles in the human body environment. It was found that P( DEGMA-co-VAG)was non-toxic at 0. 1-1 mg / m L concentrations when incubated with pig iliac endothelial cells( PIECs) for 24 h. Thus,the synthesized glycopolymers has great potential as drug delivery carriers.

关键词： thermoresponsive glycopolymer reversible additionfragmentation chain transfer(RAFT) polymerization non-toxic

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INTERACTION BETWEEN THE SURFACE GLYCOSYLATED POLYPROPYLENE MEMBRANE AND LECTIN

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Chinese Journal of Polymer Science 2008年第3期26卷 363-367页

作者：徐志康 Institute of Polymer Science and Key Laboratory of Macromolecular Synthesis and Functionalization (Ministry of Education) Zhejiang UniversityHangzhou 310027China

A glycopolymer bearing glucose residues was tethered onto the surface of polypropylene microporous membrane by UV-induced graft polymerization ofα-allyl *** A (Con A),a glucose recognizing lectin,could be specifically adsorbed to the membrane *** the other hand,the membrane surface showed no recognition ability to another lectin peanut ***,the recognition complex between the glycosylated membrane surface and Con A could be inhibited by glucose and mannose solution.T...

关键词： Affinity membrane Protein separation glycopolymer Glycosylated surface Garft polymerization Polypropylene microporous membrane

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Modification of polyfluorene nanoparticles via inclusion complexa- tion based on cyclodextrin for lectin sensing and cell imaging

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Science China Chemistry 2016年第12期59卷 1616-1620页

作者： PengfeiSun Mingchang Lin Guosong Chen Ming Jiang Key Laboratory for Organic Electronics and Information Displays&Institute of Advanced Materials(IAM) Jiangsu National Synergetic Innovation Center for Advanced Materials(SICAM)Nanjing University of Posts&TelecommunicationsNanjing 210023China State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceFudan UniversityShanghai 200433China

Currently, conjugated polymer nanoparticles are widely used with many biological applications, especially bio-imaging and labeling. Thus their modification with different biomacromolecules becomes a crucial step before various applications. In literature,this modification was normally performed via covalent bonds. To our best knowledge, modification based on inclusion complexation has not been reported. Herein, via host-guest interaction between cyclodextrin and adamantane, supramolecular modification to conjugated polyfluorene nanoparticles has been successfully achieved. The glycopolymer-modified conjugated polymer nanoparticles showed excellent binding ability to lectins, such as Galectin-3 and selective imaging behavior to Hep G2 cells.

关键词： inclusion complexation conjugated polymer nanoparticles polyfluorene glycopolymer Galectin-3

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Dendritic cells maturation facilitated by group-adjustable lipopolysaccharide analogues synthesized via RAFT polymerization

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Chinese Chemical Letters 2022年第9期33卷 4331-4334页

作者： Xingyu Heng Ruyan Feng Lijuan Zhu Liyin Yu Gaojian Chen Hong Chen College of Chemistry Chemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China Center for Soft Condensed Matter Physics and Interdisciplinary Research Soochow UniversitySuzhou 215006China

Transforming immature DCs into mature state to activate cellular immunity is a critical step in initiating immunoprophylaxis and ***(LPS)can promote DCs maturation by binding receptor on DCs surface,but their clinical application is limited due to biological *** many LPS analogues have been developed,complex synthesis and purification hinder their practical ***,we propose a novel and simple strategy to synthesize LPS analogues with adjustable structural *** monomer units similar to the key functional groups of LPS,we synthesize LPS analogues with different group ratios by RAFT *** obtained analogues have little negative effect on cell *** with LPS,the analogues show greater promoting effect on DCs *** the analogues can be applied to different scenarios since the degrees of promoting DCs maturation by LPS analogues with different group ratios are *** strategy provides a new direction for synthesizing LPS analogues,and it has the potential to produce LPS analogues on a large scale with tunable promoting DCs maturation effect.

关键词： LPS analogues glycopolymer RAFT polymerization Dendritic cells(DCs) Immune enhancement

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