用于增强乳腺癌光动力疗法的线粒体靶向和氧自给偏心中空纳米平台

IF 4.7 3区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jing Li, Yu Wang, Jun Tao, Xiaodan Su, Feipeng Zhu, Wei Lu, Xiaolin Han, Meng Dang, Lixing Weng
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引用次数: 0

摘要

光动力疗法(PDT)因其微创性和时空选择性,在肿瘤治疗中受到越来越多的关注。然而,光敏剂的靶向性差和肿瘤微环境的缺氧限制了光动力疗法的疗效。本文通过各向异性封装和水热刻蚀法制备了偏心中空介孔有机硅纳米颗粒(EHMONs),用于构建具有靶向性和缓解缺氧特性的PDT纳米平台。所制备的 EHMONs 具有独特的偏心中空结构、均匀的尺寸(300 nm)、较大的空腔和有序的介孔通道(2.3 nm)。线粒体靶向分子三苯基膦(CTPP)和光敏剂氯素 e6(Ce6)对 EHMONs 进行了修饰。载氧化合物全氟化碳(PFCs)被进一步载入 EHMONs 的内腔。溶血实验和体外毒性实验表明,EHMONs-Ce6-CTPP 具有很好的生物相容性,可以靶向三阴性乳腺癌的线粒体,从而增加光敏剂 Ce6 进入癌细胞后在线粒体的积累。具有携氧能力的 EHMONs-Ce6-CTPP@PFCs 进入癌细胞后可缓解缺氧。模型和细胞实验表明,EHMONs-Ce6-CTPP@PFCs 能产生更多的单线态氧活性氧(ROS)。因此,体外和体内实验表明,EHMONs-Ce6-CTPP@PFCs 对三阴性乳腺癌有很好的治疗效果。这项研究为提高 PDF 的有效性提供了一种靶向和载氧纳米平台的新方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy
Photodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic silica nanoparticles (EHMONs) are prepared by anisotropic encapsulation and hydrothermal etching for constructing PDT nanoplatforms with targeting and hypoxia-alleviating properties. The prepared EHMONs possess a unique eccentric hollow structure, a uniform size (300 nm), a large cavity, and ordered mesoporous channels (2.3 nm). The EHMONs are modified with the mitochondria-targeting molecule triphenylphosphine (CTPP) and photosensitizers chlorin e6 (Ce6). Oxygen-carrying compound perfluorocarbons (PFCs) are further loaded in the internal cavity of EHMONs. Hemolytic assays and in vitro toxicity experiments show that the EHMONs-Ce6-CTPP possesses very good biocompatibility and can target mitochondria of triple-negative breast cancer, thus increasing the accumulation of photosensitizers Ce6 at mitochondria after entering cancer cells. The EHMONs-Ce6-CTPP@PFCs with oxygen-carrying ability can alleviate hypoxia after entering in the cancer cell. Phantom and cellular experiments show that the EHMONs-Ce6-CTPP@PFCs produce more singlet oxygen reactive oxygen species (ROSs). Thus, in vitro and in vivo experiments demonstrated that the EHMONs-Ce6-CTPP@PFCs showed excellent treatment effects for triple-negative breast cancer. This research provides a new method for a targeting and oxygen-carrying nanoplatform for enhancing PDF effectiveness.
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来源期刊
Bioinorganic Chemistry and Applications
Bioinorganic Chemistry and Applications 化学-生化与分子生物学
CiteScore
7.00
自引率
5.30%
发文量
105
审稿时长
>12 weeks
期刊介绍: Bioinorganic Chemistry and Applications is primarily devoted to original research papers, but also publishes review articles, editorials, and letter to the editor in the general field of bioinorganic chemistry and its applications. Its scope includes all aspects of bioinorganic chemistry, including bioorganometallic chemistry and applied bioinorganic chemistry. The journal welcomes papers relating to metalloenzymes and model compounds, metal-based drugs, biomaterials, biocatalysis and bioelectronics, metals in biology and medicine, metals toxicology and metals in the environment, metal interactions with biomolecules and spectroscopic applications.
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