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Science China Chemistry 2024年第6期67卷 1881-1903页

作者： Dayang Wang Xiaohua Li Huanchen Yao Xin Liu Yan Gao Hailin Cong Bing Yu youqing shen College of Chemistry and Chemical Engineering College of Life SciencesCollege of Materials Science and EngineeringInstitute of Biomedical Materials and EngineeringQingdao UniversityQingdao266071China State Key Laboratory of Bio-Fibers and Eco-Textiles Qingdao UniversityQingdao266071China School of Materials Science and Engineering Shandong University of TechnologyZibo255000China Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineeringand Department of Chemical and Biological EngineeringZhejiang UniversityHangzhou310027China

Nanomedicine delivery technology plays an important role in modern medicine and has shown good therapeutic effects in scientific *** have the characteristics of wide sources,excellent biocompatibility,and *** addition,there are multifunctional groups on the main chain of polysaccharides,which can be surface-modified or functionalized to have targeting ability through specific sugar *** polysaccharide micelles with good biocompatibility,degradability,high safety,easy structural modification,and special core-shell structure are regarded as ideal carriers for ***,this review is focused on the hydrophobic modification designs of polysaccharides,the preparation methods and characteristics of micelles,and the applications of amphiphilic polysaccharide micelles in the field of *** is expected to provide some ideas and inspiration for the design of polysaccharide drug carriers.

关键词： polysaccharide hydrophobic modification micelle drug delivery biomedicine

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Research on GGT-responsive drug carrier with active transport effect

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Nano Research 2023年第5期16卷 7075-7084页

作者： Han Yan He Ma Bin He Bing Yu youqing shen Hailin Cong Institute of Biomedical Materials and Engineering College of Materials Science and EngineeringCollege of Chemistry and Chemical EngineeringQingdao UniversityQingdao 266071China State Key Laboratory of Bio-Fibers and Eco-Textiles Qingdao UniversityQingdao 266071China Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for BionanoengineeringDepartment of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310027China School of Materials Science and Engineering Shandong University of TechnologyZibo 255000China

Although a great quantity research has been done on cancer nano-drug carriers,how to deliver more cancer nano-drugs to tumor sites accurately and then endocytosis by cells is still a key problem in the process of cancer *** the concentration ofγ-glutamyl transpeptidase(GGT)in the microenvironment will be greatly increased when the liver,kidney,other organs become cancerous,we have designed a polymer nanomicelle as drug carrier that can respond to the GGT in the tumor *** the drug delivery system participates in blood circulation through the vascular wall cells to the tumor tissue,the overexpressed GGT on the surface of the cancer cells will recognize and cut theγ-glutamyl group on the carrier,the primary amines will be released to make the system with weak positive charge,which not only improves the carrier’s active transport ability for nanodrugs,but also improves the cell’s endocytosis ability for nano-drugs,so as to realize the release of nano-drugs in cancer ***’s more,the positive charge on the surface of the carrier also improves the permeability of the carrier in the tumor tissue,so that the cancer cells in the hypoxic area can also endocytosis drugs.

关键词： micelles enzyme response active transport endocytosis

A breathing A4 paper by in situ growth of green metal-organic frameworks for air freshening and cleaning

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Chinese Journal of Chemical Engineering 2022年第12期52卷 95-102页

作者： Bo Zhang Hongwen Chen Liming Jiang youqing shen Dan Zhao Zhuxian Zhou Key Laboratory of Biomass Chemical Engineering of Ministry of Education and Zhejiang Key Laboratory of Smart Biomaterials College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310027China Department of Polymer Science and Engineering Zhejiang UniversityHangzhou 310027China Department of Chemical&Biomolecular Engineering National University of Singapore117585Singapore Hangzhou Global Scientific and Technological Innovation Center Zhejiang UniversityHangzhou 311215China

Surface modification of natural cellulose fibers with nanomaterials is an effective strategy for producing functional textiles for multiple applications.A4-sized printing paper is a commonly used,cheap,and easily acquirable office supply which is mainly made of cellulose ***,we report green and simple nanofabrication of A4 paper to endow it with high capability for fragrance encapsulation and sustained release,and strong adsorption to indoor air *** method utilizes the sugar molecule of cellulose for in-situ growth ofγ-cyclodextrin(γ-CD)metal-organic frameworks(MOFs)on A4 *** obtainedγ-CD-MOF/A4 nanocomposites have superior specific surface area and high porous ***γ-CD-MOF/A4 nanocomposites can effectively encapsulate fragrant molecules through host-guest ***γ-CD-MOF/A4 nanocomposites also show strong absorption capability to formaldehyde and carbon dioxide through the formation of hydrogen bonding and chemical ***γ-CD-MOF/A4nanocomposites combine the advantages of both A4 paper andγ-CD-MOF,which can be used in indoor air freshening and cleaning.

关键词： Metal-organic frameworks A4 printing paper In situ synthesis Fragrance encapsulation Formaldehyde removal Carbon dioxide capture

Macrophage-evading and tumor-specific apoptosis inducing nanoparticles for targeted cancer therapy

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Acta Pharmaceutica Sinica B 2023年第1期13卷 327-343页

作者： Zimo Liu Xuefei Zhou Qi Li youqing shen Tianhua Zhou Xiangrui Liu Department of Pharmacology and Department of Gastroenterology of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China College of Chemical and Biological Engineering Zhejiang UniversityHangzhou 310027China International Institutes of Medicine The Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China Cancer Center Zhejiang UniversityHangzhou 310058China Department of Cell Biology School of MedicineZhejiang UniversityHangzhou 310058China

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical ***,administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system(MPS).In this study,we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor *** fabricated nanoparticles(TM-CQ/NPs)were coated with fibroblast cell membrane expressing tumor necrosis factor(TNF)-related apoptosis inducing ligand(TRAIL).Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages,but increased the nanoparticle uptake in tumor ***,this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death ***,the encapsulated chloroquine(CQ)further suppressed the uptake of nanoparticles by macrophages,and synergized with TRAIL to induce tumor cell *** vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer ***,our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.

关键词： TRAIL Fibroblast Nanoparticles Mononuclear phagocyte system Membrane coating Chloroquine Cancer therapy Drug delivery

The drug loading behavior of PAMAM dendrimer:Insights from experimental and simulation study

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Science China(Technological Sciences) 2023年第4期66卷 1129-1140页

作者： ZHOU LiPing LI JiaWei YU Bing ZHANG Jun HU Hao CONG HaiLin shen youqing Institute of Biomedical Materials and Engineering College of Materials Science and EngineeringQingdao UniversityQingdao 266071China State Key Laboratory of Bio-Fibers and Eco-Textiles Qingdao UniversityQingdao 266071China Beijing Key Laboratory for Bioengineering and Sensing Technology School of Chemistry and Biological EngineeringUniversity of Science and Technology BeijingBeijing 100083China School of Materials Science and Engineering China University of PetroleumQingdao 266580China Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310027China

Poly(amidoamine)(PAMAM)dendrimers are widely studied as drug vectors due to their particular structure and excellent *** molecules can be loaded in the internal cavity of dendrimers or adsorbed on the *** this paper,the interaction force and spatial configuration between PAMAM and several typical chemotherapy drugs(doxorubicin(DOX),paclitaxel(TAX),hydroxycamptothecin(HCPT))is studied by molecular dynamics(MD)*** essential parameters of dendrimers as drug carriers are analyzed by combining experiments and MD simulations,including particle size,drug loading,drug release,and *** simulation of dendrimer@drug complexes demonstrates that many cavities are semi-open,and most drug molecules are not completely *** internal structure of PAMAM dendrimers became looser with more extended nuclei,which increased the non-covalent interactions between PAMAM dendrimers and drug *** umbrella sampling simulations reveal that the change of binding energies between dendrimers and drug molecules is responsible for the variation in drug release *** study provides valuable enlightenment information for the drug loading/release of PAMAM dendrimers.

关键词： PAMAM dendrimer chemotherapy molecular dynamics simulation binding energies

“One-for-All”approach:a black technology for nanomedicine development?

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Medical Review 2023年第2期3卷 184-187页

作者： Jiajia Xiang Shiqun Shao Zhuxian Zhou youqing shen Zhejiang Key Laboratory of Smart Biomaterials and Center for Bionanoengineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhouZhejiang ProvinceChina ZJU-Hangzhou Global Scientific and Technological Innovation Center Zhejiang UniversityHangzhouZhejiang ProvinceChina Zhejiang Key Laboratory of Smart Biomaterials and Center for Bionanoengineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310027Zhejiang ProvinceChina

Cancer nanomedicines require different,even opposite,properties to voyage the cascade drug delivery process involving a series of biological *** nanomedicines can only alleviate adverse effects but cannot improve patient survival because they fail to meet all the ***,nanocarriers with synchronized functions are highly requisite to capacitate efficient drug delivery and enhanced therapeutic *** perspective article summarizes recent advances in the two main strategies for nanomedicine design,the All-in-One approach(integration of all the functions in one system)and the One-for-All approach(one functional group with proper affinity enables all the functions),and presents our views on future nanomedicine development.

关键词： cell membrane affinity clinical translation nanomedicine One-for-All transcytosis

Elastin-like polypeptide fusion for precision design of protein-polymer conjugates with improved pharmacology

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Science China Materials 2015年第10期58卷 767-768页

作者： youqing shen Center for Bionanoengineering & Key Laboratory of Biomass Chemical Engineering of Ministry of Education Department of Chemical and Biological EngineeringZhejiang University

Therapeutic proteins and peptides are characteristic by their high biological activity and specificity,but their clinical uses are bottlenecked by their poor stability,short in vivo half-life and immunogenicity[1].One typical example is recombinant human interferon alpha(IFN-α),FDA-approved and widely used in treatments of viral diseases and cancer,yet its short plasma half-life(t1/2=2-4 h)necessi-

关键词： IFN Elastin-like polypeptide fusion for precision design of protein-polymer conjugates with improved pharmacology

Facile synthesis of size-tunable stable nanoparticles via click reaction for cancer drug delivery

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Science China Chemistry 2014年第4期57卷 633-644页

作者： CAO Ming LIU XiangRui TANG JianBin SUI MeiHua shen youqing Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineering of Zhejiang University Department of Chemical and Biological Engineering Zhejiang University

The stability and size of polymeric nanoparticles are two of the most important parameters determining their pharmacokinetics and tumor/drug accumulation efficiency in cancer-drug delivery. Herein, we report a facile one-pot synthesis of crosslinked nanoparticles(CNPs) with tunable sizes and polyethylene glycol(PEG) shells via click reactions. Simply by adjusting the contents of the macromonomer(PEG monoacrylate) in its reaction with ethylene diacrylate and a crosslinker containing hexa-thiols groups, the sizes of the resulting PEGylated crosslinked nanoparticles could be easily tuned from 10 to 90 nm. These nanoparticle cores could encapsulate hydrophobic drugs such as doxorubicin(DOX), and the unreacted thiol and acrylate groups could be used for drug conjugation or labeling. Thus, the nanoparticles provide a multifunctional platform for drug delivery. In vivo studies showed that the larger nanoparticles(about 83.7 nm) had a much longer blood-circulation time and better tumor-targeting efficiency. One of our most important findings was that the drug encapsulated in the crosslinked nanoparticles, even though little was released at pH 7.4 under in vitro conditions, had much faster blood clearance than the nanoparticles' carrier, suggesting that drug release in the bloodstream was significant.

关键词：聚合物纳米粒子药物输送稳定性反应简便合成癌症可调纳米颗粒

Synthesis and Properties of a Biodegradable Dendritic Magnetic Resonance Imaging Contrast Agent

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Chinese Journal of Chemistry 2014年第1期32卷 91-96页

作者： Tingting Li Yue Qian Mingzhou Ye Jianbin Tang Hongjie Hu youqing shen Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineering and Department of Chemical and Biological Engineering Zhejiang University Hangzhou Zhejiang 310027 China Department of Radiology Sir Run Run Shaw Hospital (SRRSH) of School of Medicine Zhejiang University Hangzhou Zhejiang 310027 China Email: Jianbin Tang (jianbin@***) Hongjie Hu (hongjiehu@***)[*] Jianbin Tang Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineering and Department of Chemical and Biological Engineering Zhejiang University Hangzhou Zhejiang 310027 China Tel.: 0086-0571-87953925 Fax: 0086-0571-87953925Hongjie Hu Department of Radiology Sir Run Run Shaw Hospital (SRRSH) of School of Medicine Zhejiang University Hangzhou Zhejiang 310027 China

Novel biodegradable dendritic contrast agents (DCAs) based on polyester dendrimers were synthesized and *** DCAs were stable at acidic pH,but hydrolyzed rapidly at physiological pH,which rendered the DCA's long-term Gd3+ retention as low as that of small molecule *** longitudinal relaxivities of 10.2 to 17.5 L·mmol-1·s-1 were about 2.4 to 4.1 times higher than that of DTPA-Gd,indicating their superior contrast-enhancing capability to the clinically used contrast *** in vivo MRI study suggested that the DCA at lower generation (G2-DTPA-Gd) could effectively enhance the MRI of tumor,while the one at higher generation (G5-DTPA-Gd) showed more potential in liver imaging.

关键词： dendrimer magnetic resonance imaging biodegradable tumor imaging

Preparation and anti-tumor application of hyaluronic acid-based material for disulfide and copper ions co-delivery

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Science China(Technological Sciences) 2021年第9期64卷 2023-2032页

作者： PANG Long ZHONG Wei WANG QiuBo FENG HaoHui DONG HaoNan WANG Song CONG HaiLin shen youqing YU Bing Institute of Biomedical Materials and Engineering College of Chemistry and Chemical EngineeringCollege of Materials Science and EngineeringAffiliated Hospital of Qingdao UniversityQingdao UniversityQingdao 266071China State Key Laboratory of Bio-Fibers and Eco-Textiles Qingdao UniversityQingdao 266071China Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for BionanoengineeringDepartment of Chemical and Biological EngineeringZhejiang UniversityHangzhou310027China

Disulfide(DSF) has been proved good anti-tumor effect and even better with coadministration of Cu^(2+). In this work, we report the use of hyaluronic acid(HA) based materials to construct vectors for the delivery of both DSF and Cu^(2+). HA was firstly modified with polyethylene glycol monomethyl ether(mPEG) and polycaprolactone(PCL) to synthesize an amphiphilic polymer(HA-PEG-PCL). DSF could be loaded in the hydrophobic core and Cu^(2+) could be cooperated to the negative hydrophilic segment. The Cu^(2+) also played a role as crosslinking agent, which prevented DSF leakage prematurely, avoiding the bad side effects to normal tissues. The interaction between HA and CD44 improved the distribution of nanodrugs in tumor cells. When the nanodrugs were delivered to the cancer cell, the acidic micro-environment would separate the Cu^(2+) from the surface, leading to the disintegration of the micelles, promoting the release of DSF from the micelle core. The results of in vitro and in vivo experiments showed that the DSF and Cu^(2+) co-delivery vector constructed in this work could enhance the antitumor effect and have low biological toxicity.

关键词： hyaluronic acid disulfide Cu^(2+) cancer co-delivery