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Hyaluronidase-triggered anticancer drug and siRNA delivery from cascaded targeting nanoparticles for drug- resistant breast cancer therapy

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Nano Research 2017年第2期10卷 690-703页

作者： Jie Ding tingxizi liang Ying Zhou Zhiwei He Qianhao Min Liping Jiang Junjie Zhu State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical Engineering Nanjing University Nanjing 210093 China Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics China-America Cancer Research Institute Guangdong Medical University Dongguan 523808 China

Drug resistance renders standard chemotherapy ineffective in the treatment of connective tissue growth factor （CTGF）-overexpressing breast cancer. By co-embedding the breast tumor cell-penetrating peptide （PEGA-pVEC） and hyaluronic acid （HA） as a targeting media, novel cascaded targeting nanoparficles （HACT NPs） were created on a rattle mesoporous silica （rmSiO2） scaffold for the pinpoint delivery of siRNAs along with an anticancer drug, aiming at overcoming the drug resistance of CTGF-overexpressing breast cancer in vivo. The targeting nanoparticles selectively accumulated in the vasculature under the guidance of the PEGA-pVEC peptide, cascaded by receptor-mediated endocytosis with the aid of another targeting agent, HA, presenting a greater in vivo tumor targeting ability than single targeting ligand vectors. In addition, an HA shell prevented the leakage of therapeutic drugs during the cargo transport process, until the hyaluronidase （HAase）-triggered degradation upon lysosomes entering, guaranteeing a controllable drug release inside the target cells. When the protective shell disintegrates, the released siRNA took charge to silence the gene associated with drug resistance, CTGF, thus facilitating doxorubicin-induced apoptosis. The cascaded targeting media （PEGA-pVEC and HA） advances precision-guided therapy in vivo, while the encapsulation of siRNAs into a chemotherapy drug delivery system provides an efficient strategy for the treatment of drug resistance cancers.

关键词： drug-resistant breast cancer siRNA breast tumor cell-penetrating peptide hyaluronic acid rattle mesoporous silica

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Rationally designed approaches to augment CAR-T therapy for solid tumor treatment

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Bioactive Materials 2024年第3期33卷 377-395页

作者： Chaojie Zhu Qing Wu Tao Sheng Jiaqi Shi Xinyuan Shen Jicheng Yu Yang Du Jie Sun tingxizi liang Kaixin He Yuan Ding Hongjun Li Zhen Gu Weilin Wang Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009China liangzhu Laboratory Zhejiang University Medical CenterHangzhou311121China Department of Cell Biology School of MedicineZhejiang UniversityHangzhouZhejiang310058China Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province HangzhouZhejiang310009China ZJU-Pujian Research&Development Center of Medical Artificial Intelligence for Hepatobiliary and Pancreatic Disease HangzhouZhejiang310058China Jinhua Institute of Zhejiang University Jinhu1321299China Department of General Surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou310016China

Chimeric antigen receptor T cell denoted as CAR-T therapy has realized incredible therapeutic advancements for B cell malignancy ***,its therapeutic validity has yet to be successfully achieved in solid *** from hematological cancers,solid tumors are characterized by dysregulated blood vessels,dense extracellular matrix,and filled with immunosuppressive signals,which together result in CAR-T cells’insufficient infiltration and rapid *** insufficient recognition of tumor cells and tumor heterogeneity eventually causes cancer *** addition,CAR-T therapy also raises safety concerns,including potential cytokine release storm,on-target/off-tumor toxicities,and neuro-system side *** we comprehensively review various targeting aspects,including CAR-T cell design,tumor modulation,and delivery *** believe it is essential to rationally design a combinatory CAR-T therapy via constructing optimized CAR-T cells,directly manipulating tumor tissue microenvironments,and selecting the most suitable delivery strategy to achieve the optimal outcome in both safety and efficacy.

关键词： CAR-T therapy Cancer immunotherapy Drug delivery CAR construct design Tumor modulation Delivery strategy

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Therapeutic potential of adipose tissue

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Science Bulletin 2020年第20期65卷 1702-1704页

作者： tingxizi liang Di Wen Xintong Zhong Liping Jiang Jun-Jie Zhu Zhen Gu Department of Bioengineering.University of California Los AngelesCA 90095USA State Key Laboratory of Analytical Chemistry and Collaborative Innovation Center of Chemistry for Life Sciences School of Chemistry&Chemical EngineeringNanjing UniversityNanjing 210023China Jonsson Comprehensive Cancer Center California NanoSystems Instituteand Center for Minimally Invasive TherapeuticsUniversity of CaliforniaLos AngelesCA 90095USA

Adipose tissue is a highly specialized connective tissue that typically contributes to 10%-29%of body weight in an adult[1].Fat cells,including white adipocytes responsible for lipid storage and brown and beige adipoc... 详细信息

关键词： metabolism 脂肪组织 specialized

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