Ru@CeO2 yolk shell nanozymes: Oxygen supply in situ enhanced dual chemotherapy combined with photothermal therapy for orthotopic/subcutaneous colorectal cancer
Ru@CeO2 yolk shell nanozymes: Oxygen supply in situ enhanced dual chemotherapy combined with photothermal therapy for orthotopic/subcutaneous colorectal cancer
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Ru@CeO2蛋黄壳纳米酶：原位供氧增强双化疗联合光热疗法治疗原位/皮下结直肠癌
DOI：
10.1016/j.biomaterials.2020.119923
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发表时间：
2020
期刊：
影响因子：
14
通讯作者：
Qin Xiuying
中科院分区：
文献类型：
--
作者：
Zhu Xufeng;Gong Youcong;Liu Yanan;Yang Chunhua;Wu Sijie;Yuan Guanglong;Guo Xian;Liu Jie;Qin Xiuying
缺氧是实体瘤形成多药耐药、复发转移的重要因素。纳米酶对肿瘤微环境的响应是肿瘤特异性治疗的一种新的有效策略。本研究采用一锅法合成中空Ru@CeO2yolk壳纳米酶（Ru@CeO2YSNs），该酶具有优异的光热转化效率和催化性能。将抗肿瘤药物钌络合物（ruthenium complex， RBT）和白藜芦醇（resveratrol, Res）在Ru@CeO2YSNs中双重负载，利用聚乙二醇构建双层外层结构，形成按需释放的双药递送体系（Ru@CeO2-RBT/Res- dpeg）。双层外层结构增加了Ru@CeO2YSNs的生物相容性，有效延长了血液循环时间。Ru@CeO2-RBT/Res-DPEG催化内源性h2o2生成氧气，实现原位供氧，增强结直肠癌双化疗和光热治疗（PTT）。体外研究发现Ru@CeO2-RBT/Res-DPEG具有良好的肿瘤穿透深度和抗肿瘤作用。此外，Ru@CeO2-RBT/Res-DPEG还能缓解肿瘤缺氧，抑制原位和皮下结直肠癌的转移和复发。因此，本研究表明卵黄壳纳米酶可作为双化疗和PTT的高效协同系统杀伤肿瘤，抑制原位结直肠癌的转移和复发。
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@CeO2yolk shell nanozymes (Ru@CeO2YSNs), which possess excellent light-to-heat conversion efficiency and catalytic performance. Antitumor drug ruthenium complex (RBT) and resveratrol (Res) were dual-loaded in Ru@CeO2YSNs, 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@CeO2YSNs and effectively prolong the circulation time in blood. Ru@CeO2-RBT/Res-DPEG catalyzes endogenous H2O2to 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.