纳米药物递送系统的设计对提高抗肿瘤药物治疗效果至关重要。项目提出利用可逆共价自组装策略发展智能蛋白质纳米结构的新概念，通过构筑酶催化驱动的蛋白质纳米马达主动给药系统，提高药物递送效率和肿瘤治疗效果。本项目以铁蛋白、斑驳病毒蛋白和SP1蛋白为基元，通过自组装构筑具有氧化还原响应的双硫、双硒或双碲桥连纳米笼或封端纳米管，实现药物负载和肿瘤内可控释放。通过化学或生物法共价修饰驱动酶（过氧化氢酶CAT、葡萄糖氧化酶GOx）构建酶催化驱动的智能马达，并调节了马达主动靶向运输药物和肿瘤部位渗透滞留能力。以二氢卟吩e6（Ce6）和阿托伐醌（ATO）为药物模型进行肿瘤光动力学治疗（PDT）研究，利用马达产氧和抑制线粒体氧消耗协同改善肿瘤乏氧微环境，增强PDT抗肿瘤疗效。通过结合蛋白质组装、自驱动马达和PDT抗肿瘤的概念，为基于蛋白质纳米结构的智能纳米药物递送系统设计与研究提供理论指导和奠定技术基础。

The design of nano-drug delivery system is great essential for improving the therapeutic efficacy of antineoplastic drugs. A new concept for developing intelligent protein nanostructures via reversible covalent self-assembly strategy was proposed in this project, to construct enzyme-propelled protein nanomotors for active-drug delivery systems, which improving the drug delivery efficiency and enhancing tumor therapy. We construct redox-responsive disulfide-, diselenide- or ditelluride-containing nanocages or terminated nanotubes for drug loading and controlled release in tumor, through self-assembly of apoferritin (aFt), mottle virus (CCMV) or SP1 building blocks. Serious of enzyme-propelled protein nanomotors are further constructed by chemically or biologically modification with catalase (CAT) and glucose oxidase (GOx), which improving the ability of active-targeting drug transhipment and enhancing deep penetration and retention in tumor. Taking photosensitizer chlorin e6 (Ce6) and atovaquone (ATO) as antitumor drugs for photodynamic therapy (PDT), the tumor hypoxia could be cooperatively reversed by the oxygen (O2) production and inhibition of mitochondrial O2 consumption, which further improving antitumor therapeutic efficacy. Through combining the concepts of protein self-assembly, self-propelled nanomotor and photodynamic tumor therapy, the implementation of this project will provide theoretical guidance and technical basis for the design and study of intelligent nano-drug delivery systems based on protein superstructures.