Synergetic delivery of triptolide and Ce6 with light-activatable liposomes for efficient hepatocellular carcinoma therapy.
Synergetic delivery of triptolide and Ce6 with light-activatable liposomes for efficient hepatocellular carcinoma therapy.
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雷公藤内酯醇和 Ce6 与光激活脂质体的协同递送用于有效的肝细胞癌治疗
DOI：
10.1016/j.apsb.2021.02.001
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Yu Z
中科院分区：
文献类型：
--
作者：
Yu L;Wang Z;Mo Z;Zou B;Yang Y;Sun R;Ma W;Yu M;Zhang S;Yu Z
肝细胞癌（HCC）被认为是世界上第二大常见的主要癌症，因为它对化疗和药物的反应都很差。雷公藤甲素（Triptolide， TP）是一种二萜三氧化物，对包括肝癌在内的多种癌症具有有效的抗癌作用，是一种很有前景的治疗药物。然而，由于其全身毒性大、溶解度低、在体内消除快，其临床应用受到限制。因此，为了克服上述障碍，设计光激活脂质体（LP），结合光敏剂Ce6和化疗药物TP (TP/Ce6-LP)，以追求药物控释和协同光动力治疗HCC。由于脂质体增强的渗透性和滞留性（EPR）作用，包裹在脂质体中的TP积聚到肿瘤部位。光敏剂Ce6在激光照射下产生活性氧（ROS），进一步氧化不饱和磷脂。通过这种方式，脂质体被破坏释放TP。近红外激光照射TP/Ce6-LP （TP/Ce6-LP+L）对患者源性肝癌异种移植瘤（PDXHCC）的体内体外抗肿瘤效果最好。TP/Ce6-LP显著降低TP的副作用。此外，TP/Ce6-LP+L通过caspase-3/PARP信号通路诱导细胞凋亡。总的来说，TP/Ce6-LP+L是一种新的潜在治疗选择，可以在毒性减弱的情况下阻止HCC进展。设计了含有Ce6和雷公藤甲素的光激活脂质体（TP/Ce6- lp）用于肝细胞癌（HCC）治疗。光动力疗法（PDT）和TP可能通过caspase-3/PARP信号通路诱导PDXHCC模型细胞凋亡。
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. Photo-activatable liposomes incorporating Ce6 and triptolide (TP/Ce6-LP) for hepatocellular carcinoma (HCC) therapy were designed. Photodynamic therapy (PDT) and TP possibly induced cell apoptosis via a caspase-3/PARP signaling pathway in PDXHCC model.
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