Multimodal therapy presents one of the most promising strategies for combining multiple therapies to treat the usually complex and insidious tumor tissue. Although multifunctional nanomaterials have been designed for the construction of multimodal therapies, the generally existing inadequate coordination among components might result in low synergistic therapeutic effects and prevent the realization of their full clinical potential. Herein, inspired by the controllable “cluster bomb” model, we designed an intelligent, biocompatible, and multifunctional nanofactory system (PDA@GOx@MnO₂-PEG) that encapsulates a variety of nanoagents to achieve high destruction efficiency against tumor. The stimulus-responsive outer MnO₂ acts as the shell of “bomb” triggering the cascade catalytic reaction and forms a self-sustainable ring catalytic chain with glucose oxidase (GOx). Polydopamine (PDA) as a substrate with excellent protein carrying capacity achieves high GOx loading. Meanwhile, its efficient photothermal conversion efficiency exhibits the potential of low-temperature (∼45°C) to further enhance GOx enzymatic activity. Notably, the internal GOx is like a “sub-bomb” that is released in a controlled manner to increase the accumulation at tumor hypoxic sites, and gives full play to its glucose consumption capacity for starvation therapy under the help of sufficient oxygen and low hyperthermia. In this system, various nanoagents cooperate and advance layer by layer to fully exploit their power, forming a self-sufficient nanofactory model, and achieving excellent low-temperature photothermal-starvation synergistic therapy through a synergistic strategy. Moreover, the nanocomposite exhibits trimodal imaging capability for sensitive diagnosis and real-time monitoring of therapy. This study provides new insights for designing biocompatible and intelligent theranostic nanoplatforms to maximize the multi-modal therapeutic effect in precision medicine.

多模式治疗是结合多种疗法来治疗通常复杂且隐蔽的肿瘤组织的最有前途的策略之一。尽管多功能纳米材料被设计用于构建多模式疗法，但通常存在的成分之间协调不足可能导致协同治疗效果低，并妨碍其充分发挥临床潜力。在此，受可控“集束炸弹”模型的启发，我们设计了一种智能、生物相容性、多功能的纳米工厂系统（PDA@GOx@MnO ₂ -PEG），该系统封装了多种纳米药物，以实现对肿瘤的高杀伤效率。刺激响应的外层MnO ₂充当“炸弹”的外壳，触发级联催化反应，并与葡萄糖氧化酶（GOx）形成自持环催化链。聚多巴胺（PDA）作为具有优异蛋白质承载能力的底物，实现了高GOx负载。同时，其高效的光热转换效率表现出低温（~45°C）进一步增强GOx酶活性的潜力。值得注意的是，内部GOx就像一颗“子炸弹”，有控制地释放，增加肿瘤缺氧部位的积累，在充足的氧气和低热的帮助下，充分发挥其葡萄糖消耗能力进行饥饿疗法。在该系统中，各种纳米药剂相互配合、层层推进，充分发挥各自的威力，形成自给自足的纳米工厂模型，通过协同策略实现优异的低温光热饥饿协同治疗。此外，纳米复合材料具有三模态成像能力，可实现灵敏诊断和实时监测治疗。这项研究为设计生物相容性和智能治疗诊断纳米平台提供了新的见解，以最大限度地提高精准医学中的多模式治疗效果。