Hepatocellular carcinoma(HCC)has been known as the second common leading cancer worldwide,as it responds poorly to both chemotherapy and medication.Triptolide(TP),a diterpenoid triepoxide,is a promising treatment agen...Hepatocellular carcinoma(HCC)has been known as the second common leading cancer worldwide,as it responds poorly to both chemotherapy and medication.Triptolide(TP),a diterpenoid triepoxide,is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC.However,its clinical application has been limited owing to its severe systemic toxicities,low solubility,and fast elimination in the body.Therefore,to overcome the above obstacles,photo-activatable liposomes(LP)integrated with both photosensitizer Ce6 and chemotherapeutic drug TP(TP/Ce6-LP)was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy.The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention(EPR)effect.Under laser irradiation,the photosensitizer Ce6 generated reactive oxygen species(ROS)and further oxidized the unsaturated phospholipids.In this way,the liposomes were destroyed to release TP.TP/Ce6-LP with NIR laser irradiation(TP/Ce6-LP+L)showed the best antitumor effect both in vitro and in vivo on a patient derived tumor xenograft of HCC(PDXHCC).TP/Ce6-LP significantly reduced the side effects of TP.Furthermore,TP/Ce6-LP+L induced apoptosis through a caspase-3/PARP signaling pathway.Overall,TP/Ce6-LP+L is a novel potential treatment option in halting HCC progression with attenuated toxicity.展开更多
基金supported by China postdoctoral Science Foundation(No.2020M673026)the National Natural Science Foundation of China(Nos.81873248,81673903 and 81773642)+1 种基金Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University(Traditional Chinese Pharmacology,China),Zhejiang Chinese Medical University(No.ZYAOXZ2018014,China)State Key Laboratory of Molecular Engineering of Polymers(2019-06,Fudan University,China)
文摘Hepatocellular carcinoma(HCC)has been known as the second common leading cancer worldwide,as it responds poorly to both chemotherapy and medication.Triptolide(TP),a diterpenoid triepoxide,is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC.However,its clinical application has been limited owing to its severe systemic toxicities,low solubility,and fast elimination in the body.Therefore,to overcome the above obstacles,photo-activatable liposomes(LP)integrated with both photosensitizer Ce6 and chemotherapeutic drug TP(TP/Ce6-LP)was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy.The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention(EPR)effect.Under laser irradiation,the photosensitizer Ce6 generated reactive oxygen species(ROS)and further oxidized the unsaturated phospholipids.In this way,the liposomes were destroyed to release TP.TP/Ce6-LP with NIR laser irradiation(TP/Ce6-LP+L)showed the best antitumor effect both in vitro and in vivo on a patient derived tumor xenograft of HCC(PDXHCC).TP/Ce6-LP significantly reduced the side effects of TP.Furthermore,TP/Ce6-LP+L induced apoptosis through a caspase-3/PARP signaling pathway.Overall,TP/Ce6-LP+L is a novel potential treatment option in halting HCC progression with attenuated toxicity.
