Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China.
Harbin Medical University Cancer Hospital, Harbin, China; Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Ultrasound Med Biol. 2020 Aug;46(8):2030-2043. doi: 10.1016/j.ultrasmedbio.2020.03.030. Epub 2020 May 29.
Sono-photodynamic therapy (SPDT) activates the same photo-/sonosensitizer and exerts more marked antitumor effects than sonodynamic therapy or photodynamic therapy. We aimed to explore the utilization of curcumin (CUR)-loaded poly(L-lactide-co-glycolide) microbubble (MB)-mediated SPDT (CUR-PLGA-MB-SPDT) in HepG2 liver cancer cells. The cytotoxicity and intracellular accumulation of CUR were determined. We used 40 µM CUR as the photo-/sonosensitizer for 3 h. In a comparison of CUR-SDT or CUR-PDT, HepG2 cell viability decreased and apoptotic rate increased in CUR-SPDT. The CUR-PLGA MBs had round spheres with smooth surfaces and an average size of 3.7 µm. In CUR-PLGA MBs, drug entrapment efficiency and drug-loading capacity were 74.29 ± 2.60% and 17.14 ± 0.60%, respectively. CUR-loaded PLGA MBs (CUR-PLGA MBs) had good biocompatibility with normal L02 cells and were almost non-cytotoxic to HepG2 cells. Among CUR-SDT, CUR-PDT, CUR-SPDT or CUR-PLGA-MB-SDT, the cell CUR-PLGA-MB-SPDT had the lowest viability. Transmission electron microscopy revealed pyroptosis and apoptosis in the CUR-PLGA-MB-SPDT group; the potential mechanism was related to the mitochondrial membrane potential loss and increased production of intracellular reactive oxygen species. These findings suggested that CUR-PLGA-MB-SPDT may be a promising treatment for liver cancer.
声动力疗法（SPDT）激活相同的光/声敏剂，并比声动力疗法或光动力疗法产生更明显的抗肿瘤效果。我们旨在探索姜黄素（CUR）负载的聚（L-丙交酯-共-乙交酯）微泡（MB）介导的声动力疗法（CUR-PLGA-MB-SPDT）在 HepG2 肝癌细胞中的应用。测定 CUR 的细胞毒性和细胞内积累。我们使用 40µM CUR 作为光/声敏剂，处理 3 小时。在 CUR-SDT 或 CUR-PDT 的比较中，CUR-SPDT 使 HepG2 细胞活力降低，凋亡率增加。CUR-PLGA MB 呈圆形球体，表面光滑，平均粒径为 3.7µm。在 CUR-PLGA MB 中，药物包封效率和载药量分别为 74.29±2.60%和 17.14±0.60%。载 CUR 的 PLGA MB（CUR-PLGA MB）对正常 L02 细胞具有良好的生物相容性，对 HepG2 细胞几乎无细胞毒性。在 CUR-SDT、CUR-PDT、CUR-SPDT 或 CUR-PLGA-MB-SDT 中，细胞 CUR-PLGA-MB-SPDT 的活力最低。透射电子显微镜显示 CUR-PLGA-MB-SPDT 组发生细胞焦亡和细胞凋亡；潜在机制与线粒体膜电位丧失和细胞内活性氧产生增加有关。这些发现表明 CUR-PLGA-MB-SPDT 可能是治疗肝癌的一种有前途的方法。
