Lipid‐Coated Gold Nanoparticles Functionalized by Folic Acid as Gene Vectors for Targeted Gene Delivery in vitro and in vivo. (12th October 2017)

• Record Type: Journal Article
• Authors: Du, Baoji; Gu, Xiaoxiao; Han, Xu; Ding, Guanyu; Wang, Yuling; Li, Dan; Wang, Erkang; Wang, Jin
• Is Part Of: ChemMedChem. Volume 12:Number 21(2017)
• Page Start: 1768
• Page End: 1775
• Publication Date: 2017-10-12
• Subjects: folic acid -- gene vectors -- gold nanoparticles -- liposomes -- targeted gene transfection; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201700391
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Lipid‐based nanoparticles as gene vectors have attracted considerable attention for their high gene transfection efficiency and low cytotoxicity. In our previous work, we synthesized gold nanoparticles/dimethyldioctadecylammonium bromide (DODAB)/dioleoylphosphatidylethanolamine (DOPE) (GDD) as anionic lipid‐ and pH‐sensitive gene vectors. To further realize targeted gene transfection, a series of gold nanoparticles/DODAB/DOPE/DOPE‐folic acid (DOPE‐FA) with various ratios of DOPE‐FA were prepared and termed as GF n (for which n =1.0, 2.5, 5.0, 7.5, or 10.0 %). The gene transfection efficiency mediated by GF2.5 can reach about 85 % for MCF‐7 (FA‐receptor‐positive cells), higher than those of the negative control (GDD, 35 %) and positive control (Lipofectamine 2000, 65 %). However, GF2.5 does not further promote gene transfection into A549 (FA‐receptor‐negative cells). The higher gene transfection efficiency for MCF‐7 cells can be attributed to enhanced cellular uptake efficiency mediated by the FA targeting ability. Furthermore, GF2.5 was also found to accumulate at the specific tumor site and showed enhanced in vivo gene delivery ability. In addition, no significant harm was observed for the main tissues of the mice after treatment with GF2.5. Therefore, GF2.5, with the targeting ability and improved transfection efficiency, shows promise for its utility in gene therapy for tumor cells that overexpress FA receptors. We believe the results of this study will find more broad applications in gene therapy. Abstract : Cancer specific : We synthesized gold nanoparticles protected by folic acid (FA)‐functionalized lipids for targeted and highly efficient gene transfection. We found that such nanoparticles can significantly increase the efficiency of gene delivery with high selectivity and low toxicity by enhancing the cellular uptake into FA‐receptor‐positive tumor cells (such as MCF‐7) in vitro and in vivo, whereas they did not assist gene transfection for FA‐receptor‐negative cells (such as A549).