State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China.
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
J Control Release. 2022 Dec;352:766-775. doi: 10.1016/j.jconrel.2022.11.003. Epub 2022 Nov 10.
Colorectal cancer (CRC) is the second most deadly cancer worldwide, with chemoresistance remaining a major obstacle in CRC treatment. Sodium persulfate (NaSO) is a novel agent capable of producing •SO and Na for chemodynamic therapy (CDT). This can induce pyroptosis and ferroptosis instead of conventional apoptosis in tumor cells. Meanwhile, IR780-iodide (IR780), as an excellent phototherapy agent, can generate hyperthermia and generate a large amount of reactive oxygen species (ROS) to synergize with the CDT of NaSO, with potential to overcome chemoresistance in CRC. However, the low stability of NaSO and the poor solubility of IR780 limit their applications in the medical field. Accordingly, for the first time, D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS), NaSO and IR780 were rationally designed in a cascade-amplifying nanoplatform (NaSO-IR780 NPs) via a co-assembly strategy. Combining NaSO and IR780 in a nanoplatform improves the stability of NaSO and the solubility of IR780. As a result, the NaSO-IR780 NPs exhibited excellent antitumor efficacy in CRC cell lines and five chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models. This photo-chemodynamic nanoplatform provides a brand-new paradigm by manipulating osmolarity and redox homeostasis to overcome chemo-resistance and holds great potential for the treatment of CRC.
结直肠癌（CRC）是全球第二大致命癌症，化疗耐药仍然是 CRC 治疗的主要障碍。过硫酸钠（NaSO）是一种新型的能够产生•SO 和 Na 的化学动力学治疗（CDT）药物。它可以在肿瘤细胞中诱导细胞焦亡和铁死亡，而不是传统的细胞凋亡。同时，IR780-碘化物（IR780）作为一种优秀的光疗剂，能够产生高热并产生大量活性氧（ROS），与 NaSO 的 CDT 协同作用，有潜力克服 CRC 的化疗耐药性。然而，NaSO 的低稳定性和 IR780 的低溶解度限制了它们在医学领域的应用。因此，首次通过共组装策略，在级联放大纳米平台（NaSO-IR780 NPs）中合理设计了 D-α-生育酚聚乙二醇 1000 琥珀酸酯（TPGS）、NaSO 和 IR780。在纳米平台中结合 NaSO 和 IR780 提高了 NaSO 的稳定性和 IR780 的溶解度。结果，NaSO-IR780 NPs 在 CRC 细胞系和五种化疗耐药细胞系中表现出优异的抗肿瘤疗效，并在裸鼠异种移植模型中表现出强大的抑制能力。这种光化学动力学纳米平台通过操纵渗透压和氧化还原稳态来克服化疗耐药性，提供了一种全新的范式，为 CRC 的治疗提供了巨大的潜力。
