State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun 130022, P. R. China.
University of Science and Technology of China, Hefei 230026, P. R. China.
ACS Appl Mater Interfaces. 2021 Feb 3;13(4):4825-4834. doi: 10.1021/acsami.0c19584. Epub 2021 Jan 26.
Ultrasound (US)-induced sonodynamic therapy (SDT) is an efficient and precise method against tumor, and the integration of multiple cancer therapies has been proved as a promising strategy for better therapeutic effects. Herein, for the first time, a multifunctional nanoreactor has been fabricated by integrating Fe-MIL-88B-NH, PFC-1, and glucose oxidase (GO) to form urchin-like Fe-MIL-88B-NH@PFC-1-GO (MPG) nanoparticles as Fenton's reagent, a sonosensitizer, and a tumor microenvironment (TME) modulator. In detail, MPG can generate OH for chemodynamic therapy (CDT) and deplete glutathione (GSH) to alleviate the antioxidant ability of cancer cells. Moreover, catalase (CAT)-like MPG can react with HO to generate O for relieving hypoxia in TME, enhancing GO-catalyzed glucose oxidation to produce HO and gluconic acid. Then, the regenerated HO can promote the Fenton reaction to achieve GO catalysis-enhanced CDT. Owing to its large π-electron conjugated system, MPG also serves as an ideal sonosensitizer, realizing a burst generation of O under US irradiation for efficient SDT. Therefore, the tumor treatment will be notably enhanced by MPG-based synergetic CDT/SDT/starvation therapy via a series of cascade reactions. Overall, this work develops a versatile nanoreactor with improved tumor treatment effectiveness and broadens the application prospects of porous materials in the field of biomedical research.
超声(US)诱导的声动力学疗法(SDT)是一种针对肿瘤的高效、精确的方法,并且多种癌症疗法的联合已被证明是提高治疗效果的一种有前途的策略。在此,首次通过将 Fe-MIL-88B-NH、PFC-1 和葡萄糖氧化酶(GO)集成到一起,形成具有类刺猬状结构的 Fe-MIL-88B-NH@PFC-1-GO(MPG)纳米粒子,作为 Fenton 试剂、声敏剂和肿瘤微环境(TME)调节剂,制备了一种多功能纳米反应器。具体而言,MPG 可以产生用于化学动力学疗法(CDT)的 OH 和消耗谷胱甘肽(GSH)以减轻癌细胞的抗氧化能力。此外,具有 CAT 样活性的 MPG 可以与 HO 反应生成 O,以缓解 TME 中的缺氧,增强 GO 催化的葡萄糖氧化生成 HO 和葡萄糖酸。然后,再生的 HO 可以促进 Fenton 反应,从而实现 GO 催化增强的 CDT。由于其具有较大的π电子共轭体系,MPG 还可用作理想的声敏剂,在 US 照射下实现 O 的爆发性产生,从而高效进行 SDT。因此,通过一系列级联反应,基于 MPG 的协同 CDT/SDT/饥饿疗法将显著增强肿瘤的治疗效果。总的来说,这项工作开发了一种多功能纳米反应器,提高了肿瘤治疗效果,并拓宽了多孔材料在生物医学研究领域的应用前景。