Pancreatic cancer remains one of the most lethal malignancies worldwide.The combina-tion 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 stimuli-responsive 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 de-livery of small interference RNA(siRNA)for synergistic pancreatic cancer treatment.This"all-in-one"delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhib-itory 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 ther-apy,which represents an appealing way for pancreatic cancer treatment.

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

Department of Medical Oncology,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou 310058,China;College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;Department of Hepatobiliary and Pancreatic Surgery,the First Affiliated Hospital,Zhejiang University,Hangzhou 310003,China

药学学报（英文版）

[1]Honglin Tang;Yanan Xue;Bowen Li;Xiaojie Xu;Fu Zhang;Jiajing Guo;Qijun Li;Tingting Yuan;Yuan Chen;Yubin Pan;Yuan Ping;Da Li-.Membrane-camouflaged supramolecular nanoparticles for co-delivery of chemotherapeutic and molecular-targeted drugs with siRNA against patient-derived pancreatic carcinoma)[J].药学学报（英文版）,2022(08):3410-3426

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