Feedback enhanced tumor targeting delivery of albumin-based nanomedicine to amplify photodynamic therapy by regulating AMPK signaling and inhibiting GSTs  

作　　者：Jiaqi Huang Renjiang Kong Yanmei Li Ni Yan Yeyang Wu Ziwen Qiu Zhenming Lu Xiaona Rao Shiying Li Hong Cheng 

机构地区：[1]School of Biomedical Engineering&Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering,Southern Medical University,Guangzhou 510515,China [2]School of Pharmaceutical Sciences,Guangzhou Medical University,Guangzhou 511436,China

出　　处：《Chinese Chemical Letters》2024年第8期481-485,共5页中国化学快报（英文版）

基　　金：support of National Natural Science Foundation of China(No.52073140);the Guangdong Basic and Applied Basic Research Foundation(No.2022B1515020095).

摘　　要：Oxidative therapies receive a limited antitumor efficiency due to the insufficient reactive oxygen species(ROS)levels at focal sites and the evolvement of antioxidant defense systems.Herein,we develop an albumin-based nanomedicine to co-deliver chlorin e6(Ce6)and COH-SR4(CS),which can simultaneously enhance the yield and lethality of intracellular ROS for amplified photodynamic therapy(PDT).In which,CS acts as both an activator of AMP-activated protein kinase(AMPK)and an inhibitor of glutathione S-transferases(GSTs).Benefiting from it,the prepared HSA-Ce6@COH-SR4(HCCS)enables positive feed-back uptake by promoting AMPK phosphorylation,leading to rapid and extensive tumor accumulation of drugs.As a result,HCCS obviously increases the ROS production to elevate intracellular oxidative stress.Furthermore,HCCS can inhibit GSTs to disturb the antioxidant defense system of tumor cells,intensifying the oxidative damage of ROS.Ultimately,the PDT of HCCS is significantly strengthened by improving the ROS yield and lethality,which greatly declines the proliferation of breast cancer in vivo.This study may open a window in the development of drug co-delivery system for enhanced oxidative therapy of tumors.

关 键 词：Human serum albumin Drug delivery Reactive oxygen species Positive feedback uptake Oxidative damage 

分 类 号：R943[医药卫生—药剂学] TB383.1[医药卫生—药学]