Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
J Nanobiotechnology. 2024 Jan 3;22(1):7. doi: 10.1186/s12951-023-02268-5.
Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous HO to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous HO into O to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients.
放射性核素内放疗(RIT)是一种临床有效的癌症治疗方法,但由于肿瘤微环境(TME)的缺氧特性,其治疗效果仍不理想。过氧化氢酶(CAT)或类 CAT 纳米材料可用于酶促分解 TME 内源性 HO,以促进 TME 氧合,从而减轻肿瘤内的缺氧水平,但由于其稳定性或降解性差,缺氧缓解的持续时间较短,仍然阻碍了其有效性,无法与 RIT 的长期治疗时间相匹配。在此,我们提出了一种利用面依赖性类 CAT 的 Pd 基二维(2D)纳米平台来持续增强 RIT 的创新策略。具体而言,合理设计的 2D Pd@Au 纳米片(NSs)能够持续将内源性 HO 酶促转化为 O,从而克服缺氧诱导的 RIT 耐药性。此外,部分包覆的 Au 层赋予了近红外二区(NIR-II)响应性和适度的光热治疗,增强了它们的酶促功能。这种具有双重作用的方法为重塑 TME 铺平了道路,从而促进了近距离放射疗法对癌症的消融。我们的工作在催化纳米医学和核医学的整合方面取得了重大进展,其总体目标是放大接受 RIT 治疗的患者的临床获益。
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