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


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 ofN-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.


CONCLUSIONS
The Cur-coordinated nanoparticles developed in this study improved Cur stability, which could further release Cur in a ROS-dependent manner in cancer cells.
State Key Laboratory of Natural Medicines, Department of Pharmaceutics; Jiangsu Key Laboratory of Drug Screening; Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University.
Cheng-Qiong
CQ
Luo
State Key Laboratory of Natural Medicines, Department of Pharmaceutics; Jiangsu Key Laboratory of Drug Screening; Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University.
Lei
L
Xing
State Key Laboratory of Natural Medicines, Department of Pharmaceutics.
Peng-Fei
PF
Cui
State Key Laboratory of Natural Medicines, Department of Pharmaceutics.
Jian-Bin
JB
Qiao
State Key Laboratory of Natural Medicines, Department of Pharmaceutics.
Yu-Jing
YJ
He
Department of Hematology, The Affiliated Zhongda Hospital of Southeast University.
Bao-An
BA
Chen
State Key Laboratory of Natural Medicines, Department of Pharmaceutics; Jiangsu Key Laboratory of Drug Screening; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Liang
L
Jin
State Key Laboratory of Natural Medicines, Department of Pharmaceutics; Jiangsu Key Laboratory of Drug Screening; Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University.
Hu-Lin
HL
Jiang
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D016877:Oxidants / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016877:Oxidants; D011108:Polymers; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D003474:Curcumin
coordination; curcumin; hydrogen peroxide; phenylboronic acid; stimuli-responsive