关键词： ALT, liver-related alanine aminotransferase AST, aspartate aminotransferase BCA, bicinchoninic acid BUN, blood urea nitrogen CK, creatine kinase CK-MB, creatine kinase-MB CLSM, confocal laser scanning microscopy Ce6 Chol, cholesterol Cr, creatinine DEE, drug encapsulation efficiency DLC, drug loading content DLS, dynamic light scattering DSPG, distearoyl phosphatidylglycerole Dox, doxorubicin EPR, enhanced permeability and retention FBS, fetal bovine serum FCM, flow cytometry HCC, hepatocellular carcinoma Hepatocellular carcinoma LDH, lactate dehydrogenase LP, liposomes NIR, near-infrared PDT, photodynamic therapy PDX model PDX, patient-derived xenograft PDXHCC, patient derived tumor xenograft of HCC PI, propidium iodide Photo-activatable liposomes Photosensitizer Process of photodynamic therapy Pt, platinum ROS, reactive oxygen species So, sorafenib Synergetic delivery TEM, transmission electron microscope TP, triptolide TP/Ce6-LP, liposomes integrated with both photosensitizer Ce6 and chemotherapeutic drug TP TUNEL, dT-mediated dUTP Nick-End Labeling Triptolide

来  源：   DOI：10.1016/j.apsb.2021.02.001   PDF(Sci-hub)   PDF(Pubmed)

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.
摘要：
肝细胞癌（HCC）已被称为全球第二常见的主要癌症，因为它对化疗和药物的反应都很差。雷公藤甲素(TP),二萜三环氧化物，是一种有前途的治疗剂，因为它对包括HCC在内的多种癌症具有有效的抗癌作用。然而,由于其严重的全身毒性，其临床应用受到限制，低溶解度，在体内快速消除。因此,为了克服上述障碍，设计了光敏剂Ce6和化疗药物TP（TP/Ce6-LP）整合的可光活化脂质体（LP），以追求HCC治疗中的药物控释和协同光动力疗法。由于增强的通透性和滞留(EPR)效应,包封在脂质体中的TP积累到肿瘤部位。在激光照射下，光敏剂Ce6产生活性氧（ROS）并进一步氧化不饱和磷脂。这样,脂质体被破坏以释放TP。用NIR激光照射的TP/Ce6-LP（TP/Ce6-LPL）在体外和体内对患者来源的HCC肿瘤异种移植物（PDXHCC）均显示出最佳的抗肿瘤作用。TP/Ce6-LP可显著降低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，在停止肝癌进展与毒性减弱。
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