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Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao Jie Jiang Wei Wu Jiaqi Shi Yanfang Wang Yuejun Yao Tao Sheng Feng Liu Wei Liu Peng Zhao Feifei Lv Jie Sun Hongjun Li Zhen Gu National key laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University key laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu laboratory Zhejiang University Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University Department of laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang University moe key laboratory of macromolecular synthesis and functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

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A MONTE CARLO SIMULATION STUDY OF THE EFFECT OF CHAIN LENGTH ON THE HYDROLYSIS OF POLY(LACTIC ACID)

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Chinese Journal of Polymer Science 2013年第11期31卷 1554-1562页

作者： Zhuo-li Lin Jun Luo Zheng-jian Chen Jun Yi Hong-liang Jiang Ke-hua Tu 王利群 moe key laboratory of macromolecular synthesis and functionalization Department of Polymer Science and EngineeringZhejiang University

The intrinsic relationship between molecular chain length and the probability of chain reaction during poly（lactic acid）（PLA） hydrolysis was investigated by Monte Carlo simulation. The chain reaction rate was calculated by introducing a power function of different molecular chain lengths. The hydrolysis of both amorphous and extended-chain crystal PLA was selected as the model system. It is found that, the chain reaction probability was proportional to the chain length with a power of 0.4 for amorphous PLA and 0.7-1 for extended-chain crystal PLA, respectively. These results indicate that PLA with longer chain length usually exhibits larger reaction rate than that with shorter length. Comparing the hydrolysis of the two kinds of PLA, the competition between longer and shorter chains in the different condensed structures is different.

关键词： Monte Carlo Simulation Chain length Poly(lactic acid) Hydrolysis Molecular weight distribution.

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RHEOLOGICAL PROPERTIES OF WHEAT GLIADINS IN AQUEOUS PROPANOL

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Chinese Journal of Polymer Science 2013年第5期31卷 809-814页

作者： Shao-min Sun 宋义虎 Qiang Zheng moe key laboratory of macromolecular synthesis and functionalization Department of Polymer Science and EngineeringZhejiang University

Rheological properties of wheat gliadins in 50% （V/F） aqueous propanol were carried out as a function of gliadin concentration c and temperature. The solutions at 20 g L-1 to 200 g L-1 behave as Newtonian fluids with an flow activation energy of 23.5-27.3 kJ mol-1. Intrinsic viscosity [η] and Huggins constant kH are determined according to Huggins plot at c 〈 120 g L-1. The results reveal that gliadins are not spherical shaped and the molecular size tends to increase with temperature due to improved solvation.

关键词： Gliadin Solution Rheological properties Intrinsic viscosity.

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synthesis of Poly[6-(2,6-bis(1＇-methylbenzimidazolyl)pyridin-4-yloxy)hexyl acrylate](PBIP) and Magnetic Property of Its Neodymium Complex(PBIP-Nd^(3＋))

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Chinese Journal of Polymer Science 2016年第7期34卷 910-917页

作者： di-zheng liu 孙维林 rong ren yan-hua wang zhi-quan shen moe key laboratory of macromolecular synthesis and functionalization Department of Polymer Science and Engineering Zhejiang University Hangzhou 310027 China

Homopolymer（PBIP） containing 2,6-bis（1＇-methylbenzimidazolyl）pyridine（Me BIP） ligands in the side chain was synthesized by RAFT polymerization and its kinetics was studied. Polymeric complex PBIP-Nd^3＋ was prepared by chelating PBIP with lanthanide ion Nd^3＋. The homopolymers and PBIP-Nd^3＋ complex were investigated by NMR, FTIR, GPC and TGA. The optical property of PBIP-Nd^3＋ complex was characterized by UV-Vis spectroscopy. The magnetic property of PBIP-Nd^3＋ complex was measured as a function of temperature（5 K to 300 K） and as a function of field（-3.98×10^6 A/m to 3.98×10^6 A/m）. These results indicated that PBIP-Nd^3＋ complex is paramagnetic.

关键词： 2 6-Bis(1-methylbenzimidazolyl)pyridine Magnetic RAFT Polymeric complex Neodymium

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In-depth study on aminolysis of poly(ε-caprolactone): Back to the fundamentals

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Science China Chemistry 2012年第11期55卷 2419-2427页

作者： ZHU Yang MAO ZhengWei SHI HuaYu GAO ChangYou moe key laboratory of macromolecular synthesis and functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China

The aminolysis can effectively introduce primary amine （- quent surface fiiofunctionalization reactions. However, less NH2） groups onto polyester materials, enabling a variety of subse- attention has been paid to the basic knowledge of aminolysis reac- tion in terms of reaction kinetics and its influences on materials properties. In this study, taking the widely used poly（e-caprolactone）（PCL） as a typical example, the influences of diamines and solvent property on the surface -NH2 density are firstly assessed by using X-ray photoelectron spectroscopy （XPS） and colorimetric analysis. Results show that smaller dia- mine molecules and nonpolar alcohols could accelerate the reaction. The reaction kinetics with 1,6-hexanediamine is further investigated as a function of temperature, reaction time, and diamine concentration. During the initial stage, the reaction shows a 1^st order kinetics with the diamine concentration and has an activation energy of 54.5 kJ/mol. Ionization state of the -NH2 groups on the PCL surface is determined, revealing that the pKa of -NH3^＋（〈5） is much lower than that of the corresponding diamine molecules in solution. After aminolysis, surface hydrophilicity of PCL membrane is significantly enhanced, while surface elastic modulus and average molecular weight are decreased to some extent, and others such as weight, surface mor- phology and bulk mechanical strength are not apparently changed. The introduced -NH2 groups are found to be largely lost at 37 ℃, but can be mostly maintained at low temperature.

关键词： poly(ε-caprolactone) aminolysis surface modification biomaterials

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Ibuprofen induced drug loaded polymeric micelles

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Chinese Chemical Letters 2011年第9期22卷 1123-1126页

作者： Song Wei Tan Hong Jun Wang Ke Hua Tu Hong Liang Jiang Li Qun Wang moe key laboratory of macromolecular synthesis and functionalization Department of Polymer Science and Engineering Zhejiang UniversityHangzhou 310027 China

Three model drugs with different function groups were chosen to dialyze with dextran-graft-poly （N-isopropylacrylalaide）. Only ibuprofen could induce the formation of drug loaded micelles, which was contirmed with dynamic light scattering and transmission electron microscope. Hydrogen-bonding between the amide groups of poly （N-isopropylacrylamide） and the carboxyl groups of ibuprofen was driving force for the drug-loaded micelle. It was also found thai the diameter of the ibuprofen-loaded micelles changed reversibly against temperature.

关键词： Micellc Thernlo-sensilive Drug Hydrogen-bonding Poly (N-isopropylacryhlmide)

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Long-range ordering of composites for organic electronics:TIPS-pentacene single crystals with incorporated nano-fibers

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Chinese Chemical Letters 2017年第11期28卷 2121-2124页

作者： Huanbin Li Guobiao Xue Jiake Wu Wenqiang Zhang Zhuoting Huang Zengqi Xie Huolin L.Xin Gang Wu Hongzheng Chen Hanying Li State key laboratory of Silicon Materials MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University Institute of Polymer Optoelectronic Materials and Devices State Key Laboratory of Luminescent Materials and Devices South China University of Technology Center for functional Nanomaterials Brookhaven National Laboratory

Multi-component active materials are widely used for organic electronic devices, with every component contributing complementary and synergistic optoelectronic functions. Mixing these components generally leads to lowered crystallinity and weakened charge transport. Therefore, preparing the active materials without substantially disrupting the crystalline lattice is highly desired. Here, we show that crystallization of TIPS-pentacene from solutions in the presence of fluorescent nanofibers of a perylene bisimide derivative （PBI） leads to formation of composites with nanoflber guest incorporated in the crystal host. In spite of the binary composite structure, the TIPS-pentacene maintains the single- crystalline nature. As a result, the incorporation of the PB1 guest introduces additional fluorescence function but does not significantly reduce the charge transport property of the TIPS-pentacene host, exhibiting field-effect mobility as high as 3.34 cm^2 V^-1 s^-1 even though 26.4% of the channel area is taken over by the guest. As such, this work provides a facile approach toward high-performance multifunctional organic electronic materials.

关键词： Organic Electronics Single Crystals Composites High Mobility Field-Effect Transistors

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ROS-responsive 18β-glycyrrhetic acid-conjugated polymeric nanoparticles mediate neuroprotection in ischemic stroke through HMGB1 inhibition and microglia polarization regulation

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Bioactive Materials 2023年第1期19卷 38-49页

作者： Lulu Jin Zhixin Zhu Liangjie Hong Zhefeng Qian Fang Wang Zhengwei Mao moe key laboratory of macromolecular synthesis and functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou310027China b The moe Frontier Science Center for Brain Research and Brain-Machine Integration Zhejiang University School of Brain Science and Brain MedicineHangzhou310058China

Ischemic stroke is an acute and serious cerebral vascular disease,which greatly affects people’s health and brings huge economic burden to ***,as important innate immune components in central nervous system(CNS),are double-edged swords in the battle of nerve injury,considering their polarization between pro-inflammatory M1 or anti-inflammatory M2 *** mobility group box 1(HMGB1)is one of the potent pro-inflammatory mediators that promotes the M1 polarization of microglia.18β-glycyrrhetinic acid(GA)is an effective intracellular inhibitor of HMGB1,but of poor water solubility and dose-dependent *** overcome the shortcomings of GA delivery and to improve the efficacy of cerebral ischemia therapy,herein,we designed reactive oxygen species(ROS)responsive polymer-drug conjugate nanoparticles(DGA)to manipulate microglia polarization by suppressing the translocation of nuclear *** presented excellent therapeutic efficacy in stroke mice,as evidenced by the reduction of infarct volume,recovery of motor function,suppressed of M1 microglia activation and enhanced M2 activation,and induction of ***,our work demonstrates a close association between HMGB1 and microglia polarization,suggesting potential strategies for coping with inflammatory microglia-related diseases.

关键词： HMGB1 Microglia M1/M2 phenotype Polymer-drug conjugates Drug delivery Ischemic stroke

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Thiol-yne click polymerization

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Chinese Science Bulletin 2013年第22期58卷 2711-2718页

作者： YAO BiCheng SUN JingZhi QIN AnJun TANG Ben Zhong moe key laboratory of macromolecular synthesis and functionalization Department of Polymer Science and EngineeringZhejiang University Department of Chemistry Institute for Advanced StudyInstitute of Molecular Functional MaterialsThe Hong Kong University of Science & Technology

The research on using thiol-ene click reaction to synthesize sulfur-containing polymers with topological structures and advanced functional properties is a hot topic. However, the application of the thiol-yne reaction in the functional polymer preparation is limited and the thiol-yne click polymerization is to be further developed. In this review, we summarized recent research efforts on using thiol-yne click polymerization to synthesize polymers with topological structures. The sulfur-containing polymers were facilely prepared by photo-and thermo-initiated, amine-mediated, and transition-metal-catalyzed thiol-yne click polymerizations. These polymers are promising to be used as drug-delivery vehicles, high refractive index optical materials, photovoltaic materials, and biomaterials etc.

关键词：含硫聚合物巯基过渡金属催化拓扑结构反应合成合成聚合物功能特性应用程序

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Perylene-Based Fluorescent Sizing Agent for Precise Evaluation of Permeability and Coating Property of Sizing Paste

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Advanced Fiber Materials 2020年第5期2卷 279-290页

作者： Enqi Jin Zhengke Wang Qiaoling Hu Manli Li Jiugang Yuan moe key laboratory of macromolecular synthesis and functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China College of Textiles and Apparel Shaoxing UniversityShaoxing 312000China College of Textiles and Apparel Jiangnan UniversityWuxi 214122China

Warp sizing is considered as the most important process of weaving preparation in the textile *** quality of sized warp yarns is directly determined by the permeation and coating of sizing paste into/on warp ***,many significant flaws of the current method of permeability and coating property of sizing paste,such as low accuracy and narrow variety adaptability for sizing agents and warp yarns,have emerged in the evaluation *** order to eliminate the inherent flaws in the current method,the investigation chose chitosan(CS)as a representative of common sizing agents,introduced various amounts of perylene units onto molecular chains of the CS,and prepared a new functional sizing agent-fluorescent CS with different labeling degrees of ***,PVA-perylene was synthesized to evaluate the permeability and coating property of PVA sizing ***,three indexes to indicate the permeability and coating property of sizing paste,*** percentage,coating percentage and integrity percentage of sizing film,were evaluated using the CS-perylene and PVA-perylene derivatives *** to the fluorescence emitted by the perylene units,the three indexes can be determined accurately and conveniently depending on only fluorescent microscope and common image processing *** investigation efficiently solves the difficult problem of evaluating permeation and coating property of the pastes of both bio-based and petroleum-based sizing agents with appropriate degrees of labeling and has a significant guiding function on accurate determination of the quality of sized yarns.

关键词： Fluorescent sizing agent Perylene Chitosan PVA Permeability Coating property

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