DataSheet1_Development of A Decahedral Nanoenzyme Capable of Overcoming Hypoxia to Facilitate the Iodine-125 Radiosensitization of Esophageal Cancer.docx

Radioisotopes have long been leveraged for internal radiotherapy-mediated cancer treatment. However, such therapeutic approaches are associated with serious side effects, and their efficacy is limited by intratumoral hypoxia. Herein, we prepared a folic acid-decorated palladium decahedral platform capable of enhancing the radiotherapeutic efficacy of iodine-125 (125I) seed treatment. This decahedral nanoenzyme was able to target tumor regions and catalyze the conversion of intracellular H2O2 to O2, thereby alleviating hypoxia within the tumor microenvironment. In addition, palladium was hypoxia can be alleviated, on the other hand, palladium was able to enhance the radiotherapeutic energy deposition within tumor tissues. The results of this analysis indicated that synthesized decahedral constructs can efficiently target and modify the hypoxic tumor microenvironment while simultaneously enhancing radiation energy deposition therein. Relative to palladium nanodots, the prolonged in vivo circulation of these decahedral constructs better enabled them to facilitate sustained radiosensitization. Overall, the results of this study highlight a novel approach to improving the therapeutic utility of 125I seed interstitial implantation, thus underscoring an important direction for future clinical research.

放射性同位素（radioisotopes）长期以来被应用于内放疗介导的癌症治疗。然而，此类治疗策略往往伴随严重不良反应，且其疗效受肿瘤内缺氧的限制。本研究中，我们制备了一种叶酸修饰的钯十面体型载体（folic acid-decorated palladium decahedral platform），可提升碘-125（¹²⁵I）粒子治疗的放射疗效。该十面体型纳米酶（nanoenzyme）可靶向肿瘤区域，催化细胞内过氧化氢（H₂O₂）转化为氧气，进而缓解肿瘤微环境（tumor microenvironment）中的缺氧状态。此外，肿瘤缺氧可得到缓解；另一方面，钯基载体能够增强肿瘤组织内的放疗能量沉积（radiotherapeutic energy deposition）。本研究分析结果表明，合成的十面体型结构可高效靶向并重塑缺氧肿瘤微环境，同时在该区域增强辐射能量沉积。相较于钯纳米点（palladium nanodots），此类十面体型结构的体内循环（in vivo circulation）周期更长，更利于实现持续的放射增敏作用（radiosensitization）。总体而言，本研究结果为改善碘-125粒子组织间植入（interstitial implantation）治疗的临床效用提供了全新策略，也为未来临床研究指明了重要方向。