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Effective combination treatment of lung cancer cells by single vehicular delivery of siRNA and different kinds of anticancer drugs

Authors Li J, Wang Y, Xue S, Sun J, Zhang W, Hu P, Ji L, Mao Z

Received 27 February 2016

Accepted for publication 23 May 2016

Published 13 September 2016 Volume 2016:11 Pages 4609—4624

DOI https://doi.org/10.2147/IJN.S107345

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang


Jinming Li,* Yuanyuan Wang,* Shanshan Xue, Jinghua Sun, Wei Zhang, Ping Hu, Liangnian Ji, Zongwan Mao

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China

*These authors contributed equally to this work

Abstract: In recent years, lung cancer has become one of the fastest growing cancers in the world. Thus, the development of efficient combination therapy to treat lung cancer has attracted significant attention in the cancer therapy field. In this article, we developed a single vehicle drug delivery system, based on quantum dot (QD) nanoparticles, to deliver small interfering RNA (siRNA; target Bcl-2) and different anticancer drugs (carboplatin, paclitaxel, and doxorubicin) simultaneously for treating A549 lung cancer cells efficiently by combination therapy. The QD nanoparticles were conjugated with L-arginine (L-Arg) and different kinds of hydroxypropyl-cyclodextrins (HP-α-CDs, HP-β-CDs, and HP-γ-CDs) on the surface to form the delivery nanocarriers (QD nanocarriers). They were able to not only bind and transport the siRNA through electrostatic interactions with L-Arg residues but also accommodate various disparate anticancer drugs using different HP-CD modifications. Compared with free drug treatments, the use of QD nanocarriers to deliver Bcl-2 siRNA and different anticancer drugs simultaneously exerted a threefold to fourfold increase in cytotoxicity in A549 cells, which greatly improved the treatment efficacy through combined action. Furthermore, the QD nanocarriers could be used as a probe for real-time imaging of the drug delivery and release because of their strong fluorescence properties. These findings indicate that multifunctional QD nanocarriers hold great promise as a powerful tool for combination therapy for lung cancer.

Keywords:
combination therapy, lung cancer cells, Bcl-2 siRNA, anticancer drugs, quantum dot nanocarriers

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