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力追踪揭示转铁蛋白促进 HAIYPRH 肽偶联纳米结构细胞摄取的动态机制。

Revealing the Dynamic Mechanism by Which Transferrin Promotes the Cellular Uptake of HAIYPRH Peptide-Conjugated Nanostructures by Force Tracing.

机构信息

School of Chemistry and Life Science, Advanced Institute of Materials Science, Changchun University of Technology, Changchun 130012, China.

School of Chemical Engineering, Changchun University of Technology, Changchun 130012, China.

出版信息

Mol Pharm. 2021 Mar 1;18(3):1480-1485. doi: 10.1021/acs.molpharmaceut.0c01119. Epub 2021 Jan 31.

DOI:10.1021/acs.molpharmaceut.0c01119
PMID:33517655
Abstract

The HAIYPRH (T7) peptide has been widely used as a ligand for constructing tumor-targeted nanodrug delivery systems since it can target the transferrin receptor (TfR) and then enter cells easily with the help of transferrin (Tf). However, the dynamic mechanism by which transferrin promotes the entry of T7-conjugated nanostructures into cells remains unclear. Herein, a force tracing technique based on atomic force microscopy (AFM) was used to track the ultrafast dynamic process of a T7-conjugated gold nanoparticle (AuNP-T7) entering a cell at the single-particle level in real time. Tf helped decrease the endocytosis force and increase the endocytosis speed of AuNP-T7 in A549 cells. However, Tf only increased the endocytosis speed of AuNP-T7 in HeLa cells. In contrast, in Vero cells without TfR overexpression, Tf decreased the endocytosis speed. This report provides important insights for redesigning and developing T7-conjugated nanodrug carriers in targeted nanodrug delivery systems.

摘要

HAIYPRH(T7)肽已被广泛用作构建肿瘤靶向纳米药物输送系统的配体,因为它可以靶向转铁蛋白受体(TfR),然后在转铁蛋白(Tf)的帮助下轻松进入细胞。然而,转铁蛋白促进 T7 缀合的纳米结构进入细胞的动态机制尚不清楚。本文采用基于原子力显微镜(AFM)的力跟踪技术,实时跟踪 T7 缀合的金纳米颗粒(AuNP-T7)在单个颗粒水平上进入细胞的超快动态过程。转铁蛋白有助于降低内吞力并提高 A549 细胞中 AuNP-T7 的内吞速度。然而,转铁蛋白仅增加了 HeLa 细胞中 AuNP-T7 的内吞速度。相比之下,在没有 TfR 过表达的 Vero 细胞中,转铁蛋白降低了内吞速度。本报告为重新设计和开发靶向纳米药物输送系统中的 T7 缀合纳米药物载体提供了重要见解。

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