Nanocatalytic Tumor Therapy by Single-Atom Catalysts
Nanocatalytic Tumor Therapy by Single-Atom Catalysts
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DOI：
10.1021/acsnano.9b00457
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发表时间：
2019-02-01
期刊：
影响因子：
17.1
通讯作者：
Shi, Jianlin
中科院分区：
文献类型：
--
作者：
Huo, Minfeng;Wang, Liying;Shi, Jianlin
在肿瘤微环境（TME）中引发局部催化化学反应可以在实现高特异性和生物安全性的同时实现吸引人的肿瘤治疗效果，这主要取决于生物医学纳米催化剂的高性能。本报告表明，聚乙二醇化的单原子含铁纳米催化剂（PSAF NC）可以有效地触发原位肿瘤特异性芬顿反应，以产生大量的有毒羟基自由基（中心点OH）选择性下的酸性TME。基于密度泛函理论，从理论上揭示了纳米催化剂可以通过质子介导的H2O2均裂途径特异性催化多相芬顿反应.这些产生的自由基不仅可以导致恶性肿瘤的细胞凋亡，而且还可以诱导脂质过氧化物的积累，引起肿瘤细胞铁凋亡，这协同导致令人印象深刻的肿瘤抑制结果。同时，PSAF纳米粒良好的生物降解性和生物相容性也保证了其良好的体内外生物安全性。
Initiating localized catalytic chemical reactions in tumor microenvironment (TME) can achieve appealing tumor-therapeutic efficacy concurrently with high specificity and desirable biosafety, which is mainly dependent on the high performance of biomedical nanocatalysts. This report demonstrates that PEGylated single-atom Fe-containing nanocatalysts (PSAF NCs) could effectively trigger the in situ tumor-specific Fenton reaction to generate abundant toxic hydroxyl radicals (center dot OH) selectively under the acidic TME. Based on density functional theory, it has been theoretically uncovered that the nanocatalysts could specifically catalyze the heterogeneous Fenton reaction via a proton-mediated H2O2-homolytic pathway. These generated radicals could not only lead to the apoptotic cell death of malignant tumors, but also induce the accumulation of lipid peroxides, causing tumor cell ferroptosis, which synergistically lead to an impressive tumor suppression outcome. In the meantime, the favorable biodegradability and biocompatibility of PSAF NCs also guarantee their desirable biosafety both in vivo and in vitro.