Chitosan Stabilized Gold-Folate-Poly(lactide-co-glycolide) Nanoplexes Facilitate Efficient Gene Delivery in Hepatic and Breast Cancer Cells.
J Nanosci Nanotechnol
; 18(7): 4478-4486, 2018 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-29442622
ABSTRACT
The biodegradable polymer, poly(lactide-co-glycolide) is a popular polymer of choice in many nanotherapeutic studies. Herein, we report on the synthesis and evaluation of four chitosan stabilized poly(lactide-co-glycolide) nanoparticles with and without coating with gold, and the targeting ligand, folic acid, as potential non-viral gene delivery vectors. The poly(lactide-co-glycolide) nanoparticles were synthesized via nanoprecipitation/solvent evaporation method in conjunction with the surface functionalizing folic acid and chitosan. The physiochemical properties (morphology, particle size, zeta potential, folic acid/chitosan presence, DNA binding), and biological properties (nuclease protection, in vitro cytotoxicity and transfection potential in human kidney, hepatocellular carcinoma and breast adenocarcinoma cells), of all four gene bound nanoparticles were evaluated. Gel retardation assays confirmed that all the nanoparticles were able to successfully bind the reporter plasmid, pCMV-luc DNA at varying weight ratios. The gold-folate-poly(lactide-co-glycolide) nanoplexes with the highest binding efficiency (w/w ratio 41), best protected the plasmid DNA as evidenced from the nuclease protection assays. Furthermore, these nanoplexes presented as spherical particles with an average particle size of 199.4 nm and zeta potential of 35.7 mV. Folic acid and chitosan functionalization of the nanoparticles was confirmed by attenuated total reflection-Fourier transform infrared spectroscopy. All nanoplexes maintained over 90% cell viability in all cell lines investigated. Interestingly, the gold-folate-poly(lactide-co-glycolide) nanoplexes showed a greater transgene activity in the hepatic and breast cancer cells compared to the other nanocomplexes in the same cell lines. The favorable size, colloidal stability, low cytotoxicity, significant transgene expression, and nuclease protection ability in vitro, all provide support for the use of gold-folate-poly(lactide-co-glycolide) nanoplexes in future gene therapy applications.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Poliglicólico
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Neoplasias da Mama
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Terapia Genética
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Quitosana
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Nanopartículas
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Ácido Fólico
Limite:
Female
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Humans
Idioma:
En
Revista:
J Nanosci Nanotechnol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
África do Sul