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丝素蛋白包覆的 AuPt 双金属纳米酶的简便工程化,响应肿瘤微环境因子用于增强纳米催化治疗。

Facile engineering of silk fibroin capped AuPt bimetallic nanozyme responsive to tumor microenvironmental factors for enhanced nanocatalytic therapy.

机构信息

State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University, Chongqing 400715, China.

Cancer Center, Medical Research Institute, Southwest University, Chongqing 400716, China.

出版信息

Theranostics. 2021 Jan 1;11(1):107-116. doi: 10.7150/thno.50486. eCollection 2021.

Abstract

Reactive oxygen species (ROS), as a category of highly reactive molecules, are attractive for eliminating tumor cells . However, the intrinsic tumor microenvironment (TME) always compromises treatment efficacy. In another aspect, silk fibroin (SF), as a category of natural biomacromolecules, is highly promising for synthesis of metallic nanocrystals via biomineralization. As a proof-of-concept study, AuPt bimetallic nanozyme derived from bioinspired crystallization of chloroauric acid and chloroplatinic acid was facilely developed in the presence of silk fibroin (SF). Antitumor effects caused by the as-synthesized AuPt@SF (APS) nanozyme were demonstrated in 4T1 tumor cells and xenograft tumor models . APS nanozyme can decompose glucose to constantly supply HO and deplete intracellular glutathione (GSH). APS nanozyme can simultaneously convert adsorbed O and endogenic HO into superoxide radicals (O) and hydroxyl radical (OH), respectively, upon highly efficient catalytic reaction. Subsequently, these cytotoxic ROS cause irreversible damage to the cell membrane, nucleic acid and mitochondria of tumors. Upon fluorescence/photoacoustic (FL/PA)-imaging guidance, remarkable tumor damage based on the current nanoplatform was confirmed . The objective of our investigation is to supply more useful insights on the development of SF-based nanocatalysts, which are specifically responsive to TME for extremely efficient tumor theranostics.

摘要

活性氧(ROS)作为一类高反应性分子,因其能有效杀伤肿瘤细胞而备受关注。然而,内在的肿瘤微环境(TME)总是会影响治疗效果。另一方面,丝素蛋白(SF)作为天然生物大分子的一种,非常适合通过生物矿化来合成金属纳米晶体。作为概念验证研究,在丝素蛋白(SF)存在的情况下,通过仿生结晶法简便地制备了源自氯金酸和氯铂酸的 AuPt 双金属纳米酶。所合成的 AuPt@SF(APS)纳米酶在 4T1 肿瘤细胞和异种移植肿瘤模型中表现出抗肿瘤作用。APS 纳米酶可将葡萄糖分解为持续供应的 HO 和耗竭细胞内谷胱甘肽(GSH)。APS 纳米酶可以通过高效催化反应,分别将吸附的 O 和内源性 HO 转化为超氧自由基(O)和羟基自由基(OH)。随后,这些细胞毒性 ROS 会对肿瘤细胞的细胞膜、核酸和线粒体造成不可逆转的损伤。在荧光/光声(FL/PA)成像引导下,基于当前纳米平台的显著肿瘤损伤得到了证实。我们的研究目的是为基于 SF 的纳米催化剂的开发提供更多有用的见解,这些纳米催化剂专门针对 TME 以实现极高效的肿瘤治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c715/7681078/008a5efa390b/thnov11p0107g001.jpg

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