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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Chitosan derivatives for gene transfer: effect of phosphorylcholine and diethylaminoethyl grafts on the in vitro transfection efficiency

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Autor(es):
Dalla Picola, Isadora Pfeifer ; Shi, Qin ; Fernandes, Julio Cesar ; Petronio, Maicon Segalla ; Furuyama Lima, Aline Margarete ; de Oliveira Tiera, Vera Aparecida ; Tiera, Marcio Jose
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION; v. 27, n. 16, p. 1611-1630, 2016.
Citações Web of Science: 6
Resumo

The purpose of this work was to improve the functional properties of chitosan for gene transfer by inserting phosphorylcholine (PC) and diethylaminoethyl (DEAE) groups into the main chain. A series of derivatives containing increasing contents of DEAE and a fixed content of PC groups were synthesized and characterized, aiming to evaluate the effect of these groups on the nanoparticles' properties and the in vitro transfection efficiency. The derivatives were soluble at physiological pH levels and all derivatives were less cytotoxic than the control, the lipid lipofectamine. The obtained derivatives complexed pDNA into nanoparticles with smaller sizes and higher zeta potentials than plain chitosan. The in vitro transfection was performed with nanoparticles prepared at pH 6.3 and 7.4 and the results showed that nanoparticles prepared with derivatives containing 20% of PC groups (PC18-CH) and high degrees of substitution by DEAE (PC20-CH-DEAE(100), CH-DEAE(80,) CH-DEAE(100)) displayed the better transfection efficiencies in HeLa cells, reaching relative values comparable to lipofectamine. The most effective derivative, PC18CH, was selected for complexation with siRNA and its complexes demonstrated an in vitro knockdown efficiency highly dependent on the N/P ratio. Our combined results indicated that, by means of controlled modifications, the limitations of chitosan can be overcome to obtain more effective carriers based on chitosan, and the derivatives here studied hold potential for in vivo studies. (AU)

Processo FAPESP: 10/09651-6 - Síntese e Estudos de Transfecção de nanocarreadores sítio-dirigidos de genes
Beneficiário:Isadora Pfeifer Dalla Picola
Modalidade de apoio: Bolsas no Brasil - Doutorado