iRGD-decorated reduction-responsive nanoclusters for targeted drug delivery.

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Abstract

Herein, reduction-responsive disintegratable nanoclusters (NCs) were prepared as a novel nanovehicle for targeted drug delivery. The NCs, with a diameter of ∼170 nm, were self-assembled from hydrophobically modified and iRGD decorated hydroxyethyl starch (iRGD-HES-SS-C18). DOX was loaded into the NCs as a model drug. DOX@iRGD-HES-SS-C18 NCs can disintegrate into smaller ones and release DOX under reduction stimuli. Due to the ligand-receptor binding interactions between iRGD and integrin αV, DOX@iRGD-HES-SS-C18 NCs can specifically bind to the cell membranes of HepG-2 and 4T1 cells (integrin αV positive), resulting in enhanced cellular uptake as compared to DOX@HES-SS-C18 NCs. After cellular internalization, the NCs were transported to endosomes/lysosomes in which the reductive environment triggered the disintegration and DOX release. As a consequence, DOX@iRGD-HES-SS-C18 NCs exhibited an enhanced antitumor effect as compared to DOX@HES-SS-C18 NCs and free DOX, in an in vitro antitumor activity study. The reduction-responsive disintegratable NCs reported here were proved to be a safe and efficient nanoplatform, holding significant translation potential for tumor-targeted drug delivery.

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Journal

Journal ID (iso-abbrev): Nanoscale

Title: Nanoscale

Publisher: Royal Society of Chemistry (RSC)

ISSN (Electronic): 2040-3372

ISSN (Print): 2040-3364

Publication date (Electronic): Jun 14 2018

Volume: 10

Issue: 22

Affiliations

[1 ] Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China. zifuli@hust.edu.cn yangxl@hust.edu.cn.

[2 ] Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China. zifuli@hust.edu.cn yangxl@hust.edu.cn and National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.

[3 ] Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China. zifuli@hust.edu.cn yangxl@hust.edu.cn and National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China and Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.

[4 ] Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China. zifuli@hust.edu.cn yangxl@hust.edu.cn and National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China and Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China and Wuhan Institute of Biotechnology, High Tech Road 666, East Lake high tech Zone, Wuhan, 430040, P. R. China.

Article

DOI: 10.1039/c8nr02534g

PubMed ID: 29799599

SO-VID: 6a7768b9-7144-436c-a2ae-ff07a8bfc76a

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