School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, P.R. China.
ACS Appl Bio Mater. 2024 May 20;7(5):3306-3315. doi: 10.1021/acsabm.4c00251. Epub 2024 Apr 18.
Photodynamic therapy (PDT) and ferroptosis show significant potential in tumor treatment. However, their therapeutic efficacy is often hindered by the oxygen-deficient tumor microenvironment and the challenges associated with efficient intracellular drug delivery into tumor cells. Toward this end, this work synthesized perfluorocarbon (PFC)-modified Pluronic F127 (PFC-F127), and then exploits it as a carrier for codelivery of photosensitizer Chlorin e6 (Ce6) and the ferroptosis promoter sorafenib (Sor), yielding an oxygen self-supplying nanoplatform denoted as Ce6-Sor@PFC-F127. The PFCs on the surface of the micelle play a crucial role in efficiently solubilizing and delivering oxygen as well as increasing the hydrophobicity of the micelle surface, giving rise to enhanced endocytosis by cancer cells. The incorporation of an oxygen-carrying moiety into the micelles enhances the therapeutic impact of PDT and ferroptosis, leading to amplified endocytosis and cytotoxicity of tumor cells. Hypotonic saline technology was developed to enhance the cargo encapsulation efficiency. Notably, in a murine tumor model, Ce6-Sor@PFC-F127 effectively inhibited tumor growth through the combined use of oxygen-enhanced PDT and ferroptosis. Taken together, this work underscores the promising potential of Ce6-Sor@PFC-F127 as a multifunctional therapeutic nanoplatform for the codelivery of multiple cargos such as oxygen, photosensitizers, and ferroptosis inducers.
光动力疗法 (PDT) 和铁死亡在肿瘤治疗中显示出巨大的潜力。然而，它们的治疗效果常常受到缺氧肿瘤微环境和有效将药物递送到肿瘤细胞内的挑战的限制。为此，本工作合成了全氟碳（PFC）修饰的 Pluronic F127（PFC-F127），并将其用作共递送光敏剂氯己定 6（Ce6）和铁死亡促进剂索拉非尼（Sor）的载体，得到一种自供氧纳米平台，命名为 Ce6-Sor@PFC-F127。胶束表面的 PFC 对于有效溶解和递氧以及增加胶束表面的疏水性至关重要，从而增强了癌细胞的内吞作用。将载氧基团引入胶束中增强了 PDT 和铁死亡的治疗效果，导致肿瘤细胞的内吞作用和细胞毒性增强。开发了低渗盐水技术来提高载物的包封效率。值得注意的是，在小鼠肿瘤模型中，Ce6-Sor@PFC-F127 通过联合使用增强氧的 PDT 和铁死亡有效地抑制了肿瘤生长。综上所述，Ce6-Sor@PFC-F127 作为一种多功能治疗纳米平台，具有很大的潜力，可以共递多种载物，如氧气、光敏剂和铁死亡诱导剂。
