迄今为止恶性肿瘤的治疗依旧是世界性的难题，探索有效的肿瘤治疗策略是临床医生及科研工作者的当务之急。除肿瘤临床治疗三大“金标准”外，基于纳米技术的响应型智能纳米药物因具有可调控的“毒性开关”，表现出特异性的强毒性以精准杀伤肿瘤细胞，在实现抗肿瘤治疗效果的同时，巧妙地解决临床治疗副作用的难题。在众多的响应源中，TME内源性响应的CDT疗法因其特异选择性高、组织穿透性深、TME调节能力强和副作用低等优势在肿瘤治疗新策略中异军突起。CDT疗法藉由纳米酶的催化活性将肿瘤细胞中高表达的H2O2特异性地转化为具有强毒性的·OH，诱导肿瘤细胞凋亡而实现治疗的目的。围绕“探索高反应速率、高反应灵敏度的“两高”双金属纳米酶用于肿瘤CDT疗法”的总目标，本论文主要研究成果如下：首先“基于经典寻求突破”：以芬顿化学经典介质铁元素为基础，结合广泛用于交叉偶联反应的钯元素，通过一步高温热分解方法制备具有高反应灵敏度的铁-钯双金属纳米酶，然后利用分子动力学模拟计算揭示铁和钯组分对于芬顿反应催化效率提升的协同效应，最后负载临床化学治疗药物Adriamycin，系统地验证复合纳米酶核磁共振成像引导的化学/化学动力学联合治疗恶性实体瘤的综合性能。然后“推动突破实际应用”：以高反应灵敏度铁-钯双金属纳米酶为基础，将其和紫草素一起利用薄膜水化法制备出铁-钯双金属复合纳米脂质体。在复合纳米脂质体中，紫草素作为细胞坏死性凋亡的诱导药物，而铁-钯双金属纳米酶作为芬顿反应催化剂以诱导胞内活性氧过度表达，协同增强紫草素诱导肿瘤细胞坏死性凋亡效率，并通过进一步激活免疫反应实现抗肿瘤治疗中克服凋亡抵抗的实际应用。最后“优化应用实现升级”：将双金属纳米酶中的铁元素组分升级为铜元素，利用一步共还原策略简单、批量制备形状可控、动力学可溶铜-钯双金属纳米酶。在系统验证铜-钯双金属纳米酶合金化结构同质性的基础上，同步利用基于DFT的模拟计算证明铜-钯双金属纳米酶优异催化性能提升的机理，最后体外细胞毒性实验揭示铜-钯双金属纳米酶将在体内生物催化领域拥有巨大的应用潜力。本论文基于组分和结构调控的“两高”型双金属纳米酶制备工艺探索可为新型CDT疗法纳米介质的开发提供新的路径选择，同时基于分子动力学模拟计算双金属纳米酶的组分协同效应可为新材料的设计提供重要的指导意义，最后双金属纳米酶的优异抗肿瘤治疗效果可为高效、低毒的肿瘤治疗提供新剂型选择。

So far, the treatment of malignant tumors is still a global problem. Exploring effective tumor treatment strategies is the urgent task of clinical doctors and scientific research personnel. In addition to the three "gold standards" of clinical tumor treatment, the responsive intelligent nanomedicine based on nanotechnology owns a controllable "toxicity switch", which can regulate the specific strong toxicity of intelligent nanomedicine to kill tumor cells precisely, and cleverly solve side effects while achieving the desired antitumor effect. Among different responsive sources, CDT therapy which bases on endogenous TME response stands out for its advantages like high specificity, deep tissue penetration, strong TME regulation ability and low side effects during the tumor treatment. CDT therapy induces tumor cell apoptosis by catalytic activity of nanoenzyme to specifically convert endogenous highly expressed H2O2 in tumor cells into toxic ·OH. This study mainly focus goal of "developing the ‘two highs’ bimetallic nanoenzyme with high efficiency and high sensitivity for tumor CDT therapy":Firstly, "Basing on classic to seek breakthrough": Based on the classic medium iron element of Fenton reaction, a highly sensitive iron-palladium bimetallic nanozyme was prepared by one-step high temperature thermal decomposition method via combining with palladium element which widely used in cross coupling reaction. Then the synergistic catalytic efficiency of iron and palladium components was revealed by molecular dynamics simulation. Finally, the clinical chemotherapy drug Adriamycin was loaded to systematically verify the comprehensive performance of MRI guided chemo/chemodynamic combined therapy for malignant solid tumor.Then, "Promoting breakthrough to practical application": Based on the high sensitivity iron-palladium bimetallic nanozyme, an iron-palladium bimetallic composite liposome was prepared by film hydration method through combining with shikonin. In the composite liposomes, shikonin acts as an inducer for cell necroptosis, while iron-palladium bimetallic nanozymes are used as Fenton reaction catalysts to induce over-expression of intracellular ROS, which then cooperatively enhances shikonin-induced tumor cell necroptosis, which will activate the immune response for practical anti-tumor treatment via overcome apoptosis resistance.Finally, "Optimizing application to achieve upgrading": By upgrading the iron component in the bimetallic nanozyme to copper, a simple and batch shape-controlled and dynamic miscible copper-palladium bimetallic nanozyme was prepared by one-step co-reduction strategy. After verifying the homogeneity of the copper-palladium bimetallic nanozyme alloy structure, the simulation calculation based on DFT was used to simultaneously prove the mechanism of the excellent catalytic performance of copper-palladium bimetallic nanozyme. Finally, the in vitro cytotoxicity experiment revealed that the copper-palladium bimetallic nanozyme has great application potential in the field of in vivo biological catalysis.This study explores the preparation process of "two highs" bimetallic nanozymes based on component and structure regulation, which can provide a new path for the development of novel CDT therapy catalytic medium. And the synergistic effect of bimetallic nanozyme components verified by molecular dynamics simulation can provide important guidance for the design of new catalytic materials. Finally, the excellent antitumor treatment performance of bimetallic nanozymes can provide new dosage selection for efficient and low-toxic tumor treatment.