Abstract Combination therapy has gained great attraction as an effective strategy for the treatment of cancers. In this study, non-ionic polysorbate-based nanoparticles were prepared for combination chemo/photothermal/photodynamic cancer therapy via effective intracellular delivery of piperlongumine (PL) and indocyanine green (ICG). PL was used as a pro-oxidant drug that can induce selective apoptosis through the increase of oxidative stress in cancer cells. ICG was used as a near-infrared (NIR) light-absorbing photothermal and photodynamic agent. Non-ionic Tween 80 (T80) polysorbate was used to prepare PL- and ICG-loaded micelles with nanoscale diameters. Both PL and ICG were efficiently encapsulated in the T80-based micelles. Storage stability of ICG in aqueous solutions was greatly improved by encapsulation into the T80-based micelles. ICG-loaded T80 micelles (ICG-T80) showed higher photothermal conversion efficiency than free ICG. T80 also increased cellular uptake of ICG. Moreover, ICG-T80 showed NIR light-triggered reactive oxygen species (ROS) generation in MCF-7 human breast cancer cells, owing to the photodynamic effects of NIR light-absorbing ICG. PL-loaded T80 micelles also increased intracellular ROS levels in MCF-7 cells owing to the pro-oxidant activity of PL. In vitro study showed that ICG-T80 micelles exhibited efficient anticancer activity under NIR irradiation via combined photothermal therapy (PTT) and photodynamic therapy (PDT). PL- and ICG-loaded T80 micelles (PL-ICG-T80) further increased the cytotoxicity via combined chemo/PTT/PDT. PL-ICG-T80 also showed cancer-selective cytotoxicity. This study demonstrates that PL-ICG-T80 micelles are effective for NIR light-triggered combination chemo/PTT/PDT.

中文翻译：

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用于有效组合化学/光热/光动力疗法的非离子型聚山梨醇酯纳米粒子

摘要 联合治疗作为一种有效的癌症治疗策略受到了极大的关注。在这项研究中，通过有效细胞内递送胡椒长胺 (PL) 和吲哚菁绿 (ICG)，制备了基于非离子聚山梨醇酯的纳米颗粒，用于联合化学/光热/光动力癌症治疗。PL 被用作促氧化药物，可以通过增加癌细胞的氧化应激来诱导选择性细胞凋亡。ICG 被用作近红外 (NIR) 光吸收光热和光动力剂。非离子吐温 80 (T80) 聚山梨醇酯用于制备具有纳米级直径的 PL 和 ICG 负载胶束。PL 和 ICG 都被有效地封装在基于 T80 的胶束中。通过封装到基于 T80 的胶束中，ICG 在水溶液中的储存稳定性大大提高。负载 ICG 的 T80 胶束 (ICG-T80) 显示出比游离 ICG 更高的光热转换效率。T80 还增加了 ICG 的细胞摄取。此外，由于 NIR 光吸收 ICG 的光动力效应，ICG-T80 在 MCF-7 人乳腺癌细胞中显示出 NIR 光触发的活性氧 (ROS) 生成。由于 PL 的促氧化活性，负载 PL 的 T80 胶束还增加了 MCF-7 细胞中的细胞内 ROS 水平。体外研究表明，ICG-T80胶束通过光热疗法（PTT）和光动力疗法（PDT）在近红外辐射下表现出有效的抗癌活性。PL 和 ICG 负载的 T80 胶束 (PL-ICG-T80) 通过联合化疗/PTT/PDT 进一步增加了细胞毒性。PL-ICG-T80 还显示出癌症选择性细胞毒性。