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Nanomedicine Disrupts Stromal Barriers to Augment Drug Penetration for Improved Cancer Therapy

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Chinese Journal of Chemistry 2024年第10期42卷 1175-1189页

作者： Guo-Feng Luo Wei-Hai Chen xian-zheng zhang state Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei KeyLaboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanHubei 430079China Key Laboratoryof Biomedical Polymers of Ministry of Education&Departmentof Chemistry Wuhan UniversityWuhanHubei 430072China

Tumor stroma composing diverse extracellular matrixes(ECM)and stromal cells shapes a condensed physical barrier,which severely hampers the efficient accessibility of nanomedicine to tumor cells,especially these deep-seated in the core of *** barrier significantly compromises the antitumor effects of drug-loaded nanomedicine,revealing the remarkable importance of disrupting stromal barrier for improved tumor therapy with deep penetration *** achieve this goal,various nanoparticle-based strategies have been developed,including direct depleting ECM components via delivering anti-fibrotic agents or targeting stromal cells to suppress ECM expression,dynamic regulation of nanoparticles’physicochemical properties(i.e.,size,surface charge,and morphology),mechanical force-driven deep penetration,natural/biomimetic self-driven nanomedicine,and transcytosis-inducing *** these nanostrategies were systemically summarized in this review,and the design principles for obtaining admirable nanomedicine were *** the rapid development of nanotechnology,elaborate design of multifunctional nanomedicine provides new opportunities for overcoming the critical stromal barriers to maximize the therapeutic index of various therapies,such as chemotherapy,photodynamic therapy,and immunotherapy.

关键词： Nanomedicine Tumor stroma Deep penetration Enhanced drug perfusion Cancer therapy Drug carriers Biomaterials Nanotechnology

Bio-inspired nanoenzyme for metabolic reprogramming and antiinflammatory treatment of hyperuricemia and gout

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Science China Chemistry 2021年第4期64卷 616-628页

作者： Lu zhang Chi zhang Ze-Nan Zhuang Chu-Xin Li Pei Pan Cheng zhang xian-zheng zhang Key Laboratory of Biomedical Polymers of Ministry of Education&Department of Chemistry Wuhan UniversityWuhan 430072China

Gout,a common type of inflammatory arthritis resulting from chronic elevation of uric acid(UA)level,is usually accompanied with *** current clinical drugs for the treatment of gout and hyperuricemia are greatly restricted by their limited therapeutic efficacy,off-target toxicity and severe side ***,a neutrophil membrane(NM)-coated and cascade catalytic nanoenzyme was devised with excellent inflammation targeting,inflammatory cytokines neutralizing and UA degrading characteristics for the treatment of gout and hyperuricemia with high efficacy and *** nanoenzyme was fabricated by encapsulating uricase(UOx)and catalase(CAT)into zeolitic imidazolate framework-8(ZIF-8)and further coating it with *** NM-coated nanoenzyme inherits the antigenic exterior and cell membrane functions of neutrophils for inflammation targeting and cytokine *** and CAT encapsulated in ZIF-8 could efficiently degrade UA and eliminate hydrogen peroxide(H_(2)O_(2))via a biocatalytic cascade,thus successfully blocking the inflammation amplification during gout *** in vitro and in vivo experiments demonstrated the preferable potentials of the nanoenzyme for gout targeting,inflammation elimination and UA degradation,exhibiting great promise for the treatment of gout and hyperuricemia in an effective and safe manner.

关键词： gout hyperuricemia neutrophil membrane uric acid inflammation

Tumor Cell Membrane-Coated Liquid Metal Nanovaccine for Tumor Prevention

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Chinese Journal of Chemistry 2020年第6期38卷 595-600页

作者： Yu zhang Miao-Deng Liu Chu-Xin Li Bin Li xian-zheng zhang Key Laboratory of Biomedical Polymers of Ministry of Education&Department of Chemistry Wuhan UniversityWuhanHubei 430072China

Herein,we report on a tumor nanovaccine LMNP@CM that enhances the process of antigen-presenting by stimulating the immune system to uptake tumor antigens *** nanovaccine is comprised of polyethylene glycol modified liquid metal nanoparticles(LMNP)and tumor cell membra nes(CM)as *** 808 nm irradiation,the photothermal con version effect of injected LMNP can cause mild local inflammation,and subsequently induces antigen-presenting cells active recruitment and facilitates cellular uptake of tumor ***,because of the immune adjuvant effect of metal materials,the nanovaccine LMNP@CM promotes the maturation and activation of antigen-presenting cells and induces anti-tumor immune response *** priming the host immune recognition of tumor antigens,this nanovaccine displays prophylactic effects and significantly suppresses tumor growth in a mouse breast tumor *** nanovaccine LMNP@CM represents a novel strategy of utilizing light-controlled means to actively induce anti-tumor immune processes,showing advanced therapeutic potentials and robust adaptability for treating multiple tumors by changing the loaded antigens.

关键词： vaccine inflammation utilizing

Antibacterial Sutures Coated with Smooth Chitosan Layer by Gradient Deposition

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Chinese Journal of Polymer Science 2022年第9期40卷 1050-1061页

作者： Ying-Ge Chen Chu-Xin Li Yu zhang Yong-Dan Qi Jun Feng xian-zheng zhang Key Laboratory of Biomedical Polymers of Ministry of Education&Department of Chemistry Wuhan UniversityWuhan 430072China

Owing to the significant importance in clinics,antibacterial activity is thought as one indispensable feature of the next generation of absorbable *** is challenging but imperative to arm the existing absorbable sutures with antibacterial *** present study describes a“gradient deposition”technique to coat a continuous and smooth layer of chitosan on the surface of absorbable ***,chitosan solution is arranged to undergo gradient pH decline step by step while during each pH interval,the solution is allowed to stand for a predetermined period of time in order to control gradual chitosan *** nanoparticles are found to be first generated on suture surface and finally developed into a smooth chitosan layer as the antibacterial *** vitro and in vivo results demonstrated that coating chitosan on sutures by our technique could relieve wound inflammation,stimulate collagen deposition,regenerate blood vessels,and assist tissue repairing,consequently leading to a significant enhancement of wound healing *** technique is highlighted with low cost,extreme convenience and excellent safety without organic ***,the“gradient deposition”technique would not affect the fundamental properties of matrix and thus hold promises as a universal way for superficial antibacterial modification towards almost all the surgical implanted materials,including but not limited to absorbable sutures.

关键词： Antibacterial sutures Gradient deposition Chitosan coating Wound healing Bacterial infection

Local T regulatory cells depletion by an integrated nanodrug system for efficient chem-immunotherapy of tumor

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Science China Chemistry 2019年第9期62卷 1230-1244页

作者： Fan Gao Qian Cheng Miao-Deng Liu Lei Rong Chuan-Jun Liu xian-zheng zhang Key Laboratory of Biomedical Polymers of Ministry of Education Department of ChemistryWuhan University

T regulatory(Treg) cell is a major immunosuppressive factor that restrains the antitumor effect of immunotherapy, because it gets more after the immune activation and is hardly to be eliminated. Here, an acid-sensitive integrated nanodrug system is designed to activate antitumor immune response as well as locally deplete Treg cells with low side effect. The nanosystem is synthetized by coordinating doxorubicin(DOX) and pentoxifylline(PTX) with Zn ions, then stabilized via liposome encapsulation(denoted as DTX@Lipo). DTX@Lipo can activate antitumor immune effect by chemotherapy of DOX. Besides, the release of PTX inhibits c-Rel expression, leading to the reduction of Treg cells in tumor site. Owing to the good tumor accumulation and local drug release ability, DTX@Lipo exhibits better biosafety and convenience than traditional antibody blockade method for Treg cells depletion. According to the results of in vivo experiments, the nanodrug system can significantly increase the ratio between effector T(Teff) cells and Treg cells locally, resulting in an immunoactivated tumor microenvironment. Importantly, it exhibits significant antitumor effect when combined with PD-1 blockade therapy, providing great potential for tumor therapy.

关键词： tumor T regulatory cell nanodrug system PD-1 immune response

Light-driven biohybrid system utilizes N2 for photochemical CO2 reduction

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National Science Review 2023年第7期10卷 159-171页

作者： Jin-Yue Zeng Xiao-Shuang Wang Xin-Hua Liu Qian-Ru Li Jun Feng xian-zheng zhang Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry Wuhan University Wuhan Research Centre for Infectious Diseases and Cancer Chinese Academy of Medical Sciences

Attempting to couple photochemical CO2reduction with N2fixation is usually difficult,because the reaction conditions for these two processes are typically ***,we report that a light-driven biohybrid system can utilize abundant,atmospheric N2to produce electron donors via biological nitrogen fixation,to achieve effective photochemical *** biohybrid system is constructed by incorporating molecular cobalt-based photocatalysts into N2-fixing *** is found that N2-fixing bacteria can convert N2into reductive organic nitrogen and create a localized anaerobic environment,which allows the incorporated photocatalysts to continuously perform photocatalytic CO2reduction under aerobic ***,the light-driven biohybrid system displays a high formic acid production rate of over 1.41×10-14mol h-1cell-1under visible light irradiation,and the organic nitrogen content undergoes an over-3-fold increase within 48 *** work offers a useful strategy for coupling CO2conversion with N2fixation under mild and environmentally benign conditions.

关键词： biohybrid photocatalysis CO2 reduction nitrogen fixation bacterium

Hydrogen peroxide detection with high specificity in living cells and inflamed tissues

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Regenerative Biomaterials 2016年第4期3卷 217-222页

作者： Lei Rong Chi zhang Qi Lei Ming-Ming Hu Jun Feng Hong-Bing Shu Yi Liu xian-zheng zhang Department of Chemistry Key Laboratory of Biomedical Polymers of Ministry of Education State Key Laboratory of Virology College of Life SciencesWuhan UniversityWuhanP.R.China

Hydrogen peroxide(H2O2)detection in biological systems is of significant importance,which act as critical second messenger in fundamental biological ***,we report on a chemoselective fluorescent naphthylimide peroxide probe(NPP)for the H_(2)O_(2)detection in vitro and in *** is a phenylboronic acid-caged chromophore that selectively responds to H_(2)O_(2)through a selfimmolate *** exhibited high sensitivity and selectivity to H_(2)O_(2)with distinctive fluorescence change due to the excellent two-photon excitation property,which permits the facile detection of inflammation produced H_(2)O_(2)and offers chance to monitor the inflammatory stages in diseased cells.

关键词： hydrogen peroxide fluorescence imaging inflammation

Vascular disrupting agent-induced amplification of tumor targeting and prodrug activation boosts anti-tumor efficacy

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Science China Chemistry 2022年第10期65卷 1994-2004页

作者： Sheng Hong Qian-Xiao Huang Ping Ji Xuan Pang Yunxia Sun Si-Xue Cheng xian-zheng zhang Xuesi Chen Key Laboratory of Biomedical Polymers of Ministry of Education Department of ChemistryWuhan UniversityWuhan 430072China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China

Vadimezan,one of the typical vascular disrupting agents(VDAs) currently in clinical trials,has been extensively implemented for cancer research,whereas its clinical efficacy is adversely affected by the inevitable side *** by Vadimezaninduced intratumoral coagulation activation and hypoxia aggravation,we report a strategy by utilizing these biological effects to achieve targeted delivery and activation of hypoxia-activated prodrug(HAP) thus to maximize the therapeutic effect of *** encapsulating HAP tirapazamine into poly(lactic-co-glycolic acid)(PLGA) nanocarriers along with the modification of clot-binding peptide,the obtained nanoplatform could target tumors under the coagulation activation effect of ***,the aggravated hypoxia tumor microenvironment induced by Vadimezan can also boost hypoxia-activated *** the murine tumor model,this strategy showed 80.0% suppression of tumor growth,indicating its great potential in tumor *** study offers an ingenious tactic for the combination of vascular disrupting therapy and hypoxia-activated chemotherapy,which may open up a window of the VDAs-based combination therapy.

关键词： tumor therapy prodrug vascular disrupting agent tirapazamine hypoxia

Analysis of debris flow control effect and hazard assessment in Xinqiao Gully,Wenchuan M_(s)8.0 earthquake area based on numerical simulation

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China Geology 2024年第2期7卷 248-263页

作者： Chang Yang Yong-bo Tie xian-zheng zhang Yan-feng zhang Zhi-jie Ning Zong-liang Li Chinese Academy of Geological Sciences Beijing 100037China Chengdu Center of China Geological Survey China Geological SurveyChengdu 610081China Technology innovation center for risk prevention and mitigation of geohazard Ministry of Natural ResourcesChengdu 611734China Observation and Research Station of Chengdu Geological Hazards Ministry of Natural ResourcesChengdu 610000China

Xinqiao Gully is located in the area of the 2008 Wenchuan M_(s)8.0 earthquake in Sichuan province,*** on the investigation of the 2023"6-26"Xinqiao Gully debris flow event,this study assessed the effectiveness of the debris flow control project and evaluated the debris flow *** field investigation and numerical simulation methods,the indicators of flow intensity reduction rate and storage capacity fullness were proposed to quantify the effectiveness of the engineering measures in the debris flow *** simulation results show that the debris flow control project reduced the flow intensity by41.05%to 64.61%.The storage capacity of the dam decreases gradually from upstream to the mouth of the gully,thus effectively intercepting and controlling the debris *** evaluating the debris flow of different recurrence intervals,further measures are recommended for managing debris flow events.

关键词： Landslide Debris flow Hazard assessment Numerical simulation OpenLISEM Prevention and control project Wenchuan M_(s)8.0 earthquake Xinqiao Gully Sichuan province Geological hazards survey engineering