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基于 808nm 光辐照下的单个纳米平台实现靶向线粒体一氧化碳递药和单线态氧产生以用于协同抗癌治疗。

Mitochondria-targeted carbon monoxide delivery combined with singlet oxygen production from a single nanoplatform under 808 nm light irradiation for synergistic anticancer therapy.

机构信息

Key Laboratory for Advanced Materials, School of Chemistry & Molecular Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.

Key Lab of Resource Chemistry of MOE & Shanghai Key Lab of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, P. R. China.

出版信息

J Mater Chem B. 2021 May 26;9(20):4241-4248. doi: 10.1039/d1tb00478f.

DOI:10.1039/d1tb00478f
PMID:34008693
Abstract

A multifunctional nanoplatform (1), MnCO@TPP@C-TiO2, which consists of a carrier of carbon-doped TiO2 nanoparticles with surface covalent functionalization of manganese carbonyls and a directing group of triphenylphosphine, was prepared for mitochondria-targeted carbon monoxide (CO) delivery combined with photodynamic therapy (PDT). MnCO@TPP@C-TiO2 selectively localized in the mitochondria of HeLa cells where the overexpressed-H2O2 triggered CO release resulting in mitochondrial damage. And singlet oxygen species generated upon 808 nm near infrared light irradiation further destroyed the mitochondria and induced cancer cells apoptosis. Cytotoxicity assays revealed that the nanoplatform with mitochondria-targeted CO delivery and PDT exhibited the highest lethality against cancer cells in comparison with all the other control samples tested, and it showed good dark biocompatibility with normal cells that express low H2O2 levels. This work may provide new insights into combining CO-based gas therapy with traditional PDT for efficient cancer treatment.

摘要

一种多功能纳米平台(1),MnCO@TPP@C-TiO2,由表面共价功能化的锰羰基和三苯基膦导向基团的掺碳 TiO2 纳米颗粒载体组成,用于靶向线粒体的一氧化碳(CO)输送,结合光动力疗法(PDT)。MnCO@TPP@C-TiO2 选择性地定位于 HeLa 细胞的线粒体中,其中过表达的 H2O2 触发 CO 释放,导致线粒体损伤。并且,在 808nm 近红外光照射下产生的单线态氧物种进一步破坏线粒体并诱导癌细胞凋亡。细胞毒性试验表明,与所有其他测试的对照样品相比,具有靶向线粒体 CO 输送和 PDT 的纳米平台对癌细胞表现出最高的致死性,并且它与表达低 H2O2 水平的正常细胞具有良好的暗生物相容性。这项工作可能为将基于 CO 的气体治疗与传统 PDT 相结合以有效治疗癌症提供新的见解。

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