Biocompatible and colloidally stabilized mPEG-PE/calcium phosphate hybrid nanoparticles loaded with siRNAs targeting tumors
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Pei Gao1,2, Xiangyu Zhang2, Hongzhi Wang1, Qinghong Zhang1, He Li3,*, Yaogang Li1,*, Yourong Duan2,*
1State Key Laboratory for Modification of Chemical Fibres and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China
2State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
3Traditional Chinese Medicine Department, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Yourong Duan, e-mail: [email protected]
Yaogang Li, e-mail: [email protected]
He Li, e-mail: [email protected]
Keywords: calcium phosphate, nanoparticle, siRNA delivery, biocompatible
Received: August 11, 2015 Accepted: November 16, 2015 Published: November 28, 2015
Calcium phosphate nanoparticles are safe and effective delivery vehicles for small interfering RNA (siRNA), as a result of their excellent biocompatibility. In this work, mPEG-PE (polyethylene glycol-L-α-phosphatidylethanolamine) was synthesized and used to prepare nanoparticles composed of mPEG-PE and calcium phosphate for siRNA delivery. Calcium phosphate and mPEG-PE formed the stable hybrid nanoparticles through self-assembly resulting from electrostatic interaction in water. The average size of the hybrid nanoparticles was approximately 53.2 nm with a negative charge of approximately −16.7 mV, which was confirmed by dynamic light scattering (DLS) measurements. The nanoparticles exhibited excellent stability in serum and could protect siRNA from ribonuclease (RNase) degradation. The cellular internalization of siRNA-loaded nanoparticles was evaluated in SMMC-7721 cells using a laser scanning confocal microscope (CLSM) and flow cytometry. The hybrid nanoparticles could efficiently deliver siRNA to cells compared with free siRNA. Moreover, the in vivo distribution of Cy5-siRNA-loaded hybrid nanoparticles was observed after being injected into tumor-bearing nude mice. The nanoparticles concentrated in the tumor regions through an enhanced permeability and retention (EPR) effect based on the fluorescence intensities of tissue distribution. A safety evaluation of the nanoparticles was performed both in vitro and in vivo demonstrating that the hybrid nanoparticle delivery system had almost no toxicity. These results indicated that the mPEG-PE/CaP hybrid nanoparticles could be a stable, safe and promising siRNA nanocarrier for anticancer therapy.
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