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A novel redox-sensitive system based on single-walled carbon nanotubes for chemo-photothermal therapy and magnetic resonance imaging

Authors Hou L, Yang X, Ren J, Wang Y, Zhang H, Feng Q, Shi Y, Shan X, Yuan Y, Zhang Z

Received 16 October 2015

Accepted for publication 6 December 2015

Published 5 February 2016 Volume 2016:11 Pages 607—624

DOI https://doi.org/10.2147/IJN.S98476

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Lei Yang


Lin Hou,1,2 Xiaomin Yang,1 Junxiao Ren,1 Yongchao Wang,1 Huijuan Zhang,1 Qianhua Feng,1 Yuyang Shi,1 Xiaoning Shan,1 Yujie Yuan,1 Zhenzhong Zhang1,2

1School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People’s Republic of China; 2Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, People’s Republic of China

Abstract: Recently, nanomaterials with multiple functions, such as drug carrier, magnetic resonance imaging (MRI) and optical imaging, and photothermal therapy, have become more and more popular in cancer research. In this work, a novel redox-sensitive system constructed from hyaluronic acid (HA), single-walled carbon nanotubes (SWCNTs), doxorubicin (DOX), and gadolinium (Gd) was successfully developed. Herein, HA-modified SWCNTs (SWCNTs-HA) was first synthesized, and then DOX was conjugated with HA by disulfide bond (SWCNTs-HA-ss-DOX). Finally, MRI contrast agents, Gd3+-ion loading occurred through the sidewall defects of SWCNTs, whose cytotoxicity could be sequestered within the SWCNTs. In vitro release of DOX showed that this system accomplished much faster drug release under reducing condition. Confocal microscopy analysis confirmed that Gd/SWCNTs-HA-ss-DOX were capable of simultaneously delivering DOX and SWCNTs into Michigan Cancer Foundation-7 cells via HA receptor-mediated endocytosis followed by rapid transport of cargoes into the cytosol. Enhanced cytotoxicity of Gd/SWCNTs-HA-ss-DOX further proved that the sensitive system was more potent for intracellular drug delivery as compared with the insensitive control. Meanwhile, tumor cell killing potency was improved when Gd/SWCNTs-HA-ss-DOX were combined with near-infrared irradiation, with IC50 of 0.61 µg/mL at 48 hours. In vivo investigation demonstrated that Gd/SWCNTs-HA-ss-DOX could effectively accumulate in tumor sites and possessed the greatest synergistic antitumor efficacy, especially under the 808 nm laser irradiation. More importantly, this system could be used as a contrast agent for MRI to identify the location and extent of tumor tissues. These results suggested that Gd/SWCNTs-HA-ss-DOX might be a promising system for targeting chemo-photothermal therapy and MRI diagnosis in future clinical anticancer applications.

Keywords: redox-responsive, tumor targeting, cancer diagnosis, synergistic effect, multifunctional

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