Luo Kexin, You Sasha, Chen Jingyu, Ye Wang, Tian Jian, Feng Xiyue, Wang Yingxi, Li Ling, Yu Xiaolan
Hubei Key Laboratory for Precision Synthesis of Small Molecule Pharmaceuticals & Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules & Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry, Hubei University, Wuhan 430062, China.
State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan 430062, China.
Biomater Adv. 2025 Oct;175:214336. doi: 10.1016/j.bioadv.2025.214336. Epub 2025 May 9.
Stimulating the immunogenic cell death (ICD) effect is a method of tumor treatment through activating immunity. While conventional approaches including chemotherapy, photothermal therapy (PTT), and chemodynamic therapy (CDT), demonstrate partial ICD induction capabilities, their efficacy in eliciting systemic immune responses remains constrained by the immunosuppressive tumor microenvironment. Herein, a trimetallic nanozyme (Mn/Fe-MIL-101/CuS/DOX@FA) was engineered through the integration of Mn-doped Fe-MOFs, CuS, doxorubicin (DOX, 35.08 mg/g), and folic acid (FA). The design leverages the synergistic effects of Mn(II), Fe(III), and Cu(II), combined with the photothermal performance of CuS, which collectively enhance glutathione peroxidase (GPx)-like and peroxidase (POD)-like activities. This catalytic cascade depletes glutathione and boosts hydroxyl radicals via Fenton-like reactions, thereby disrupting redox balance to amplify chemodynamic therapy. CuS-mediated photothermal effects coupled with pH/GSH-responsive DOX release further augment ICD, effectively reversing immunosuppression. In vivo evaluations demonstrated 57 % inhibition of the primary tumor and 66.7 % inhibition of the distant tumor, confirming its efficacy in tumor treatment and prevention of recurrence/metastasis. Besides, magnetic resonance imaging experiments showed the T/T dual-mode imaging performance. Thereby, a long-term anti-tumor nanoplatform is constructed through dual-mode imaging-guided multimodal therapy, which integrates tumor diagnosis, treatment, and prevention of recurrence and metastasis.
刺激免疫原性细胞死亡（ICD）效应是一种通过激活免疫来治疗肿瘤的方法。虽然包括化疗、光热疗法（PTT）和化学动力疗法（CDT）在内的传统方法显示出部分诱导ICD的能力，但其引发全身免疫反应的功效仍受到免疫抑制性肿瘤微环境的限制。在此，通过整合锰掺杂的铁基金属有机框架（Mn-doped Fe-MOFs）、硫化铜（CuS）、阿霉素（DOX，35.08 mg/g）和叶酸（FA）构建了一种三金属纳米酶（Mn/Fe-MIL-101/CuS/DOX@FA）。该设计利用了Mn(II)、Fe(III)和Cu(II)的协同效应，结合CuS的光热性能，共同增强谷胱甘肽过氧化物酶（GPx）样和过氧化物酶（POD）样活性。这种催化级联反应通过类芬顿反应消耗谷胱甘肽并促进羟基自由基的产生，从而破坏氧化还原平衡以放大化学动力疗法。CuS介导的光热效应与pH/谷胱甘肽响应性DOX释放进一步增强ICD，有效逆转免疫抑制。体内评估显示对原发性肿瘤的抑制率为57%，对远处肿瘤的抑制率为66.7%，证实了其在肿瘤治疗和预防复发/转移方面的功效。此外，磁共振成像实验显示了T1/T2双模成像性能。因此，通过双模成像引导的多模态疗法构建了一种长期抗肿瘤纳米平台，该疗法整合了肿瘤诊断、治疗以及预防复发和转移。
