Luo Kexin, You Sasha, Chen Jingyu, Chi Bin, Zhang Kai, Tian Jian, Feng Xiyue, Ye Wang, Wang Yingxi, Li Ling, Yu Xiaolan, Wang Jing
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, P. R. 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.
J Mater Chem B. 2025 Jul 2;13(26):7691-7704. doi: 10.1039/d5tb00686d.
Traditional tumor treatments focus on treating the location of the lesion, while immunogenic cell death (ICD) triggers systemic anti-tumor immunity and inhibits tumor metastasis. Therefore, there is a need to develop an inducer that amplifies ICD. Here, methotrexate (MTX) and MoO were loaded into a Cu-doped iron-based targeted metal-organic framework Fe-NH-MIL-101 with nano-enzymatic activity to establish a novel ICD amplifier. The photothermal agent MoO generates heat under near-infrared (NIR) light excitation, inducing tumor ablation. Simultaneously, the released Mo combines with Fe and Cu in the system, synergistically enhancing electron transfer efficiency based on the bimetallic system. Combined with thermal effects, this approach cooperatively elevates glutathione peroxidase (GPx)-like and peroxidase (POD)-like activities. This catalytic cascade depletes glutathione through Fenton-like reactions while amplifying hydroxyl radical (˙OH) generation, thereby remodeling the tumor microenvironment (TME), potentiating chemodynamic therapy (CDT), and triggering ICD. The chemotherapeutic agent MTX not only exerts direct cytotoxic effects but also serves as an inducer of ICD. and experiments have shown that the resulting synergistic treatment model based on the combination of CDT, photothermal therapy (PTT), and chemotherapy guided by T-MRI imaging will amplify the ICD effect, enhance tumor treatment, and is expected to achieve the prevention of metastasis and recurrence of tumors and to realize the integration of tumor diagnosis, treatment, and prevention.
传统的肿瘤治疗方法侧重于治疗病变部位，而免疫原性细胞死亡（ICD）可触发全身性抗肿瘤免疫并抑制肿瘤转移。因此，需要开发一种能够放大ICD的诱导剂。在此，将甲氨蝶呤（MTX）和MoO负载到具有纳米酶活性的铜掺杂铁基靶向金属有机框架Fe-NH-MIL-101中，以建立一种新型的ICD放大器。光热剂MoO在近红外（NIR）光激发下产生热量，诱导肿瘤消融。同时，释放出的Mo与体系中的Fe和Cu结合，基于双金属体系协同提高电子转移效率。结合热效应，这种方法协同提高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，同时放大羟基自由基（˙OH）的生成，从而重塑肿瘤微环境（TME），增强化学动力疗法（CDT），并触发ICD。化疗药物MTX不仅发挥直接的细胞毒性作用，还作为ICD的诱导剂。 实验表明，基于T-MRI成像引导的CDT、光热疗法（PTT）和化疗相结合所产生的协同治疗模型将放大ICD效应，增强肿瘤治疗效果，并有望实现肿瘤转移和复发的预防，以及肿瘤诊断、治疗和预防的一体化。
