Cocktail hepatocarcinoma therapy by a super-assembled nano-pill targeting XPO1 and ATR synergistically  

作　　者：Liuyun Gong Yinliang Lu Jing Wang Xinyue Li Jing Zhao Yuetong Chen Rongze Ma Jinlu Ma Tianya Liu Suxia Han 

机构地区：[1]Department of Radiation Oncology,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an,710061,China [2]National&Local Joint Engineering Research Center of Biodiagnosis and Biotherapy,The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an,710004,China [3]Department of Radiotherapy,The First Affiliated Hospital Soochow University,Suzhou,Jiangsu,215000,China

出　　处：《Journal of Pharmaceutical Analysis》2023年第6期603-615,共13页药物分析学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.:81272488 and 81602802);the Shaanxi Province Innovation Capacity Support Program(Grant No.:2018TD-002).

摘　　要：Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a peptide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97110 amino acids of apoptin(AP)(AA@G))was constructed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced combination therapy.

关 键 词：Liver cancer Drug combination Cancer therapy ATR inhibitor XPO1 inhibitor 

分 类 号：R96[医药卫生—药理学]