Systemic delivery of gemcitabine analogue and STAT3 siRNA promotes antitumor immunity against melanoma

作     者：Huan Yan Zhanyan Liu Guibin Lin Fei Gu Yan Liu Yuxiao Xu Xueli Kuang Yuan Zhang Huan Yan;Zhanyan Liu;Guibin Lin;Fei Gu;Yan Liu;Yuxiao Xu;Xueli Kuang;Yuan Zhang

作者机构：School of Biomedical Sciences and EngineeringSouth China University of TechnologyGuangzhou International CampusGuangzhou 511442China National Engineering Research Center for Tissue Restoration and ReconstructionSouth China University of TechnologyGuangzhou 510006China Guangdong Provincial Key Laboratory of Biomedical EngineeringSouth China University of TechnologyGuangzhou 510006China Key Laboratory of Biomedical Materials and Engineering of the Ministry of EducationSouth China University of TechnologyGuangzhou 510006China 

出 版 物：《Nano Research》 (纳米研究（英文版）)

年 卷 期：2022年第15卷第10期

页      面：9057-9072页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the Basic and Applied Basic Research Foundation of Guangdong Province(No.2020A1515111204) the Fundamental Research Funds for the Central Universities(No.2020ZYGXZR099) the Recruitment Program of Global Experts,the National Natural Science Foundation of China(No.82172080) 

主　　题：immunosuppression tumor microenvironment nanoparticle gemcitabine STAT3 siRNA 

摘      要：Immunosuppressive myeloid cells in the tumor microenvironment(TME)inhibit T-cell-mediated immune response and promote tumor *** targeting both tumor cells and myeloid cells such as myeloid-derived suppressor cells(MDSCs),is expected to promote antitumor ***(Gem)can serve as a chemotherapeutic drug and a MDSCdepleting *** activation of STAT3 promotes tumor cell growth and orchestrates the immunosuppressive activity of tumor-associated myeloid *** we describe a strategy to kill tumor cells as well as inhibit the expansion and suppressive function of myeloid cells through the systemic delivery of gemcitabine monophosphate(GMP)and STAT3 siRNA(siSTAT3).To enhance their in vivo delivery efficiency,we formulate GMP and siSTAT3 into a lipid-coated calcium phosphate(LCP)nanoparticle and a liposome-protamine-hyaluronic acid(LPH)nanoparticle,*** to the control and monotherapy groups,combined GMP and siSTAT3 nanoparticles effectively induced tumor cell death,downregulated a wide range of pro-tumor signaling pathways and immunosuppressive mediators,eliminated MDSCs,enhanced T cell effector functions in tumors and lymphoid compartments,and led to superior therapeutic efficacy in a syngeneic mouse melanoma ***,these nanoparticles can serve as adjuvant treatment to improve the therapeutic response of anti-PD-1-based immune checkpoint blockade ***,the combination of gemcitabine chemotherapy and STAT3 inhibition through nanotechnology could effectively kill tumor cells,alleviate the immunosuppressive TME,and enhance endogenous antitumor immunity.