title: Biocompatible and colloidally stabilized mPEG-PE/calcium phosphate hybrid nanoparticles loaded with siRNAs targeting tumors.
abstract: 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.
authors.affiliation: State Key Laboratory for Modification of Chemical Fibres and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.|State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Modification of Chemical Fibres and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Modification of Chemical Fibres and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Traditional Chinese Medicine Department, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory for Modification of Chemical Fibres and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
authors.forename: Yaogang
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China.
authors.forename: Yourong
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000009:adverse effects*; D001692:Biological Transport; D002130:Calcium Phosphates / Q000008:administration & dosage / Q000009:adverse effects*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D004337:Drug Carriers; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C020243:calcium phosphate
keywords: biocompatible; calcium phosphate; nanoparticle; siRNA delivery