Abstract：
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.
摘要：
光动力疗法（PDT）和铁中毒在肿瘤治疗中显示出重要的潜力。然而,它们的治疗效果通常受到缺氧的肿瘤微环境和与有效的细胞内药物递送到肿瘤细胞相关的挑战的阻碍.为此，这项工作合成了全氟化碳（PFC）改性的PluronicF127（PFC-F127），然后将其用作共同递送光敏剂Chlorine6（Ce6）和铁凋亡促进剂索拉非尼（Sor）的载体，产生表示为Ce6-Sor@PFC-F127的氧自供应纳米平台。胶束表面的PFCs在有效溶解和输送氧气以及增加胶束表面的疏水性方面发挥着至关重要的作用。引起癌细胞内吞作用增强。将携氧部分掺入胶束中增强了PDT和铁凋亡的治疗效果，导致肿瘤细胞的内吞作用和细胞毒性扩增。开发了低渗盐水技术以提高货物包封效率。值得注意的是,在小鼠肿瘤模型中，Ce6-Sor@PFC-F127通过联合使用氧增强的PDT和铁凋亡有效抑制肿瘤生长。一起来看,这项工作强调了Ce6-Sor@PFC-F127作为一种多功能治疗纳米平台的潜力，用于共同递送多种货物，如氧气，光敏剂，和铁性凋亡诱导剂。
