title: Multifunctional PEI-entrapped gold nanoparticles enable efficient delivery of therapeutic siRNA into glioblastoma cells.
abstract: RNA interference (RNAi) has been considered as a promising strategy for effective treatment of cancer. However, the easy degradation of small interfering RNA (siRNA) limits its extensive applications in gene therapy. For safe and effective delivery of siRNA, a novel vector system possessing excellent biocompatibility, highly efficient transfection efficiency and specific targeting properties has to be considered. In this study, we report the use of polyethyleneimine (PEI)-entrapped gold nanoparticles (Au PENPs) modified with an arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide via a poly(ethylene glycol) (PEG) spacer as a vector for Bcl-2 (B-cell lymphoma-2) siRNA delivery to glioblastoma cells. The synthesized Au PENPs were well characterized. The efficiency of siRNA delivery was appraised by flow cytometry, confocal microscopy imaging, and the protein expression level. Our results revealed that the Au PENPs were capable of delivering Bcl-2 siRNA to glioblastoma cells with an excellent transfection efficiency, leading to specific gene silencing in the target cells (22% and 25.5% Bcl-2 protein expression in vitro and in vivo, respectively) thanks to the RGD peptide-mediated targeting pathway. The designed RGD-targeted Au PENPs may hold great promise to be used as a novel vector for specific cancer gene therapy applications.
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn.
authors.forename: Lingdan
authors.initials: L
authors.lastname: Kong
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn.
authors.forename: Jieru
authors.initials: J
authors.lastname: Qiu
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Radiology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 100 Haining Road, Shanghai 200080, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn.
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn and CQM-Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal.
authors.forename: Xiangyang
authors.identifier: http://orcid.org/0000-0001-6785-6645
authors.initials: X
authors.lastname: Shi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D018613:Microscopy, Confocal; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D006046:Gold; D011094:Polyethyleneimine