Mitochondria-targeted carrier-free nanoparticles based on dihydroartemisinin against hepatocellular carcinoma  

作　　者：Zhiyu Yu Xiang Luo Cheng Zhang Xin Lu Xiaohui Li Pan Liao Zhongqiu Liu Rong Zhang Shengtao Wang Zhiqiang Yu Guochao Liao 

机构地区：[1]Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China,International Institute for Translational Chinese Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510006,China [2]Guangzhou Yuemei Pharmaceutical Technology Co.,Ltd.,Guangzhou 510535,China [3]Afiliated Foshan Maternity&Child Healthcare Hospital,Southern Medical University,Foshan 528000,China [4]School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China [5]Department of Laboratory Medicine,Dongguan Institute of Clinical Cancer Research,Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors,The Tenth Afiliated Hospital of Southern Medical University(Dongguan People's Hospital),Dongguan 523058,China

出　　处：《Chinese Chemical Letters》2024年第10期329-333,共5页中国化学快报（英文版）

基　　金：funded and supported by the Department of Science and Technology of Guangdong Province(No.2022B1111020005);Key Laboratory of Guangdong Provincial Food and Drug Administration(No.2021ZDB03);the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,No.2020B1212030006);Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(No.Guochao Liao,2019);Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515130005,2022A1515110270,202201011563);The Bureau of Science and Technology of Guangzhou City(No.HMJH_(2)019000)。

摘　　要：Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS)and resultant mitochondrial damage.However,clinical translation is limited by several drawbacks,such as insolubility,instability and low bioavailability.Here,based on a nanomedicine-based delivery strategy,we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP),aiming to improve bioavailability and mitochondrial targeting.DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized.Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS,which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway,leading to apoptosis.In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma.These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.

关 键 词：Hepatocellular carcinoma Carrier-freenanoparticles DIHYDROARTEMISININ Mitochondria targeting Apoptosis 

分 类 号：TB383.1[一般工业技术—材料科学与工程] R283.6[医药卫生—中药学]