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Synergetic delivery of triptolide and Ce6 with light-activatable liposomes for efficient hepatocellular carcinoma therapy

引用

Acta Pharmaceutica Sinica B 2021年第7期11卷 2004-2015页

作者： Ling Yu Zhenjie Wang Zhuomao Mo Binhua Zou Yuanyuan Yang Rui Sun Wen Ma Meng Yu Shijun Zhang Zhiqiang Yu Department of Traditional Chinese Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China The People’s Hospital of Gaozhou Maoming 525200China School of Pharmaceutical Sciences Guangdong Provincial Key Laboratory of New Drug ScreeningSouthern Medical UniversityGuangzhou 510515China

Hepatocellular carcinoma(HCC)has been known as the second common leading cancer worldwide,as it responds poorly to both chemotherapy and ***(TP),a diterpenoid triepoxide,is a promising treatment agent for its effective anticancer effect on multiple cancers including ***,its clinical application has been limited owing to its severe systemic toxicities,low solubility,and fast elimination in the ***,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 *** TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention(EPR)*** laser irradiation,the photosensitizer Ce6 generated reactive oxygen species(ROS)and further oxidized the unsaturated *** this way,the liposomes were destroyed to release ***/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/Ce6-LP+L induced apoptosis through a caspase-3/PARP signaling ***,TP/Ce6-LP+L is a novel potential treatment option in halting HCC progression with attenuated toxicity.

关键词： Hepatocellular carcinoma Synergetic delivery Triptolide Ce6 Photo-activatable liposomes Photosensitizer process of photodynamic therapy PDX model

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