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Curcumin-coordinated nanoparticles with improved stability for reactive oxygen species-responsive drug delivery in lung cancer therapy

Authors Luo CQ, Xing L, Cui P-F, Qiao JB, He YJ, Chen BA, Jin L, Jiang HL

Received 18 September 2016

Accepted for publication 30 November 2016

Published 25 January 2017 Volume 2017:12 Pages 855—869

DOI https://doi.org/10.2147/IJN.S122678

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun


Cheng-Qiong Luo,1–3,* Lei Xing,1–3,* Peng-Fei Cui,1 Jian-Bin Qiao,1 Yu-Jing He,1 Bao-An Chen,4 Liang Jin,1,2,5 Hu-Lin Jiang1–3

1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, 2Jiangsu Key Laboratory of Drug Screening, 3Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, 4Department of Hematology, The Affiliated Zhongda Hospital of Southeast University, 5School of Life Science and Technology, China Pharmaceutical University, Nanjing, China

*These authors contributed equally to this work

Background: The natural compound curcumin (Cur) can regulate growth inhibition and apoptosis in various cancer cell lines, although its clinical applications are restricted by extreme water insolubility and instability. To overcome these hurdles, we fabricated a Cur-coordinated reactive oxygen species (ROS)-responsive nanoparticle using the interaction between boronic acid and Cur.
Materials and methods: We synthesized a highly biocompatible 4-(hydroxymethyl) phenylboronic acid (HPBA)-modified poly(ethylene glycol) (PEG)-grafted poly(acrylic acid) polymer (PPH) and fabricated a Cur-coordinated ROS-responsive nanoparticle (denoted by PPHC) based on the interaction between boronic acid and Cur. The mean diameter of the Cur-coordinated PPHC nanoparticle was 163.8 nm and its zeta potential was –0.31 mV. The Cur-coordinated PPHC nanoparticle improved Cur stability in physiological environment and could timely release Cur in response to hydrogen peroxide (H2O2). PPHC nanoparticles demonstrated potent antiproliferative effect in vitro in A549 cancer cells. Furthermore, the viability of cells treated with PPHC nanoparticles was significantly increased in the presence of N-acetyl-cysteine (NAC), which blocks Cur release through ROS inhibition. Simultaneously, the ROS level measured in A549 cells after incubation with PPHC nanoparticles exhibited an obvious downregulation, which further proved that ROS depression indeed influenced the therapeutic effect of Cur in PPHC nanoparticles. Moreover, pretreatment with phosphate-buffered saline (PBS) significantly impaired the cytotoxic effect of Cur in A549 cells in vitro while causing less damage to the activity of Cur in PPHC nanoparticle.
Conclusion: The Cur-coordinated nanoparticles developed in this study improved Cur stability, which could further release Cur in a ROS-dependent manner in cancer cells.

Keywords: coordination, curcumin, phenylboronic acid, stimuli-responsive, hydrogen peroxide

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