Membrane-camouflaged supramolecular nanoparticles for co-delivery of chemotherapeutic and molecular-targeted drugs with siRNA against patient-derived pancreatic carcinoma

作     者：Honglin Tang Yanan Xue Bowen Li Xiaojie Xu Fu Zhang Jiajing Guo Qijun Li Tingting Yuan Yuan Chen Yubin Pan Yuan Ping Da Li Honglin Tang;Yanan Xue;Bowen Li;Xiaojie Xu;Fu Zhang;Jiajing Guo;Qijun Li;Tingting Yuan;Yuan Chen;Yubin Pan;Yuan Ping;Da Li

作者机构：Department of Medical OncologySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310058China College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Hepatobiliary and Pancreatic Surgerythe First Affiliated HospitalZhejiang UniversityHangzhou 310003China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2022年第12卷第8期

页      面：3410-3426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：the National Key Research and Development Program of China (No.2018YFA0901800) Natural Science Foundation of Zhejiang Province (Distinguished Young Scholar Program,No.LR21H300002,China) National Natural Science Foundation of China (Nos.81573003 and 32000992) Chinese Society of Clinical Oncology (CSCO) oncology research foundation (Nos.Y-XD2019-243 and Y-Roche2019/2-0042) Joint Foundation of Zhejiang Natural Science FoundationZhejiang Society for Mathematical Medicine (LSY19H160005,China) the Chinese Postdoctoral Science Foundation (2018M642469) Scientific Research Fund of Zhejiang Provincial Education Department (Y202148347,China) 

主　　题：Chemotherapy Target therapy siRNA Nanomedicine Hybrid membrane Drug antagonism Pancreatic carcinoma Patient-derived tumor 

摘      要：Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine(GEM) with the molecular-targeted drug erlotinib(Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuliresponsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA(siRNA) for synergistic pancreatic cancer treatment. This “all-in-onedelivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor(PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.