Development of a multi-level pH-responsive lipid nanoplatform for efficient co-delivery of si RNA and small-molecule drugs in tumor treatment  

作　　者：Yunjie Dang Yanru Feng Xiao Chen Chaoxing He Shujie Wei Dingyang Liu Jinlong Qi Huaxing Zhang Shaokun Yang Zhiyun Niu Bai Xiang 

机构地区：[1]Department of Pharmaceutics,Hebei Medical University,Shijiazhuang 050017,China [2]Department of Pharmacy,The Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China [3]Core Facilities and Centers,Hebei Medical University,Shijiazhuang 050017,China [4]Department of Hematology,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,China

出　　处：《Chinese Chemical Letters》2024年第12期265-272,共8页中国化学快报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.81973251 and 81302725);Hebei Province Funding Project for Introduced Overseas Personnel(Nos.C20230351 and C20220345);Key Research and Development Program of Hebei Province(No.22372701D);Hebei Province Natural Science Fund(No.H2020206610);Hebei Provincial Health Commission Government-Funded Clinical Medicine Talent Program(No.ZF2024048);Hebei Medical University Undergraduate Innovative Experiment Program(No.USIP2023008)。

摘　　要：The combination of nucleic acid and small-molecule drugs in tumor treatment holds significant promise;however,the precise delivery and controlled release of drugs within the cytoplasm encounter substantial obstacles,impeding the advancement of formulations.To surmount the challenges associated with precise drug delivery and controlled release,we have developed a multi-level p H-responsive co-loaded drug lipid nanoplatform.This platform first employs cyclic cell-penetrating peptides to exert a multi-level pH response,thereby enhancing the uptake efficiency of tumor cells and endow the nanosystem with effective endosomal/lysosomal escape.Subsequently,small interferring RNA(siRNA)complexes are formed by compacting siRNA with stearic acid octahistidine,which is capable of responding to the lysosome-tocytoplasm pH gradient and facilitate siRNA release.The siRNA complexes and docetaxel are simultaneously encapsulated into liposomes,thereby creating a lipid nanoplatform capable of co-delivering nucleic acid and small-molecule drugs.The efficacy of this platform has been validated through both in vitro and in vivo experiments,affirming its significant potential for practical applications in the co-delivery of nucleic acids and small-molecule drugs.

关 键 词：Cyclic peptides siRNA Liposomal platform Multi-level pH-responsive CO-DELIVERY 

分 类 号：R73-36[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]