Synergetic delivery of triptolide and Ce6 with light-activatable liposomes for efficient hepatocellular carcinoma therapy |
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| Authors: | Ling Yu Zhenjie Wang Zhuomao Mo Binhua Zou Yuanyuan Yang Rui Sun Wen Ma Meng Yu Shijun Zhang Zhiqiang Yu |
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| Institution: | aDepartment of Traditional Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;bThe People''s Hospital of Gaozhou, Maoming 525200, China;cSchool of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou 510515, China |
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| Abstract: | 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 anti-tumor 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.KEY WORDS: Hepatocellular carcinoma, Synergetic delivery, Triptolide, Ce6, Photo-activatable liposomes, Photosensitizer, Process of photodynamic therapy, PDX model |
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