Zhu Xianyu, Gao Lingli, Zheng Yanbo, Zhao Peng Fei, Wei Hanrui, Liu Ruixue, Zhao Liping, Zhang Junyi, Sun Qi, Zheng Lingling, Lv Han, Yang JiGang, Gong Jianhua, Wang Zhenchang
Precision and Intelligence Medical Imaging Lab, Beijing Friendship Hospital, Capital Medical University, 95 Yong'an Rd., Xicheng Dist., Beijing, 100050, China.
Beijing Clinical Research Institute, 95 Yong'an Rd., Xicheng Dist., Beijing, 100050, China.
Adv Healthc Mater. 2025 Jun;14(16):e2405229. doi: 10.1002/adhm.202405229. Epub 2025 Mar 24.
Poor prognosis and chemotherapy response stem from difficulties in precise targeting and the lack of effective synergistic treatments. Nanozymes show promising potential in tumor chemodynamic therapy (CDT) by catalyzing hydrogen peroxide (H₂O₂) decomposition and glutathione depletion in the tumor microenvironment (TME). However, integrating precise chemotherapy targeting with CDT remains challenging. In this study, a porous Fe/Cu bimetallic nanozyme carrier (FeCuNPs) is developed for co-loading with the humanized 3F8 anti-GD2 disialoganglioside antibody (3F8) and the novel pyridazinone-based chemotherapeutic agent (IMB), forming a nanoreactor (3F8@FeCuNPs@IMB) for targeted chemotherapy and CDT. The nanoreactor responds specifically to the acidic TME as a primary insurance, allowing for the controlled release of IMB at the tumor site. The targeting antibody 3F8 coating on the surface of the nanozyme carrier acts as a secondary insurance, minimizing chemotherapy drug leakage during the delivery process and ensuring precise targeting for effective chemotherapy. Furthermore, FeCuNPs act as peroxidase-like (POD) and glutathione oxidase-like (GSHOX) enzymes, catalyzing hydroxyl radical (•OH) generation and depleting excess GSH, enhancing CDT. The results in vitro and in vivo indicate that the dual insurance designed 3F8@FeCuNPs@IMB offers a promising prospect for a targeted, precise, and effective combination of chemotherapy and CDT against melanoma.
预后不良和化疗反应不佳源于精确靶向的困难以及缺乏有效的协同治疗方法。纳米酶通过催化肿瘤微环境（TME）中过氧化氢（H₂O₂）的分解和谷胱甘肽的消耗，在肿瘤化学动力疗法（CDT）中显示出有前景的潜力。然而，将精确的化疗靶向与CDT相结合仍然具有挑战性。在本研究中，开发了一种多孔铁/铜双金属纳米酶载体（FeCuNPs），用于与人源化3F8抗GD2二唾液酸神经节苷脂抗体（3F8）和新型哒嗪酮基化疗药物（IMB）共负载，形成用于靶向化疗和CDT的纳米反应器（3F8@FeCuNPs@IMB）。该纳米反应器作为主要保障，对酸性TME具有特异性响应，允许IMB在肿瘤部位可控释放。纳米酶载体表面的靶向抗体3F8涂层作为次要保障，使化疗药物在递送过程中的泄漏最小化，并确保精确靶向以实现有效的化疗。此外，FeCuNPs作为类过氧化物酶（POD）和类谷胱甘肽氧化酶（GSHOX），催化羟基自由基（•OH）的产生并消耗过量的GSH，增强CDT。体外和体内结果表明，双重保障设计的3F8@FeCuNPs@IMB为针对黑色素瘤的化疗和CDT的靶向、精确和有效联合提供了有前景的前景。
