Hypoxia is an important factor in forming multidrug resistance, recurrence and metastasis in solid tumors. Nanozymes respond to tumor microenvironment for tumor-specific treatment is a new and effective strategy. In this study, one-pot method was used to synthesize hollow Ru@CeO₂ yolk shell nanozymes (Ru@CeO₂ YSNs), which possess excellent light-to-heat conversion efficiency and catalytic performance. Antitumor drug ruthenium complex (RBT) and resveratrol (Res) were dual-loaded in Ru@CeO₂ YSNs, and a double outer layer structure using polyethylene glycol was constructed to form dual-drug delivery system (Ru@CeO₂-RBT/Res-DPEG) that was released on demand. The double outer layer structure increased the biocompatibility of Ru@CeO₂ YSNs and effectively prolong the circulation time in blood. Ru@CeO₂-RBT/Res-DPEG catalyzes endogenous H₂O₂ to produce oxygen, which achieve in situ oxygen supply and enhanced dual-chemotherapy and photothermal therapy (PTT) for colorectal cancer. In vitro studies found that Ru@CeO₂-RBT/Res-DPEG has good tumor penetration depth and antitumor effect. In addition, Ru@CeO₂-RBT/Res-DPEG can alleviate tumor hypoxia, and inhibit metastasis and recurrence of orthotopic and subcutaneous colorectal cancer. Accordingly, the study shows that yolk shell nanozymes can be used as an efficient synergistic system for dual-chemotherapy and PTT to kill tumor and inhibit orthotopic colorectal cancer metastasis and recurrence.

缺氧是实体瘤形成多药耐药、复发和转移的重要因素。纳米酶响应肿瘤微环境进行肿瘤特异性治疗是一种新的有效策略。本研究采用一锅法合成了空心Ru@CeO ₂蛋黄壳纳米酶（Ru@CeO ₂ YSNs），该纳米酶具有优异的光热转换效率和催化性能。将抗肿瘤药物钌配合物（RBT）和白藜芦醇（Res）双重负载在Ru@CeO ₂ YSNs中，并构建聚乙二醇双外层结构，形成双药物递送系统（Ru@CeO ₂ -RBT/Res） -DPEG）按需发布。双外层结构增加了Ru@CeO ₂ YSNs的生物相容性，有效延长了在血液中的循环时间。 Ru@CeO ₂ -RBT/Res-DPEG催化内源性H ₂ O ₂产生氧气，实现原位供氧，增强结直肠癌的双化疗和光热治疗（PTT）。体外研究发现Ru@CeO ₂ -RBT/Res-DPEG具有良好的肿瘤穿透深度和抗肿瘤作用。此外，Ru@CeO ₂ -RBT/Res-DPEG可以缓解肿瘤缺氧，抑制原位和皮下结直肠癌的转移和复发。因此，研究表明，蛋黄壳纳米酶可以作为双化疗和PTT的有效协同系统来杀死肿瘤并抑制原位结直肠癌转移和复发。