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 th...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.展开更多
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)+3 种基金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)。
文摘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.
