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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Dalla Picola, Isadora Pfeifer ; Shi, Qin ; Fernandes, Julio Cesar ; Petronio, Maicon Segalla ; Furuyama Lima, Aline Margarete ; de Oliveira Tiera, Vera Aparecida ; Tiera, Marcio Jose
Total Authors: 7
Document type: Journal article
Source: JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION; v. 27, n. 16, p. 1611-1630, 2016.
Web of Science Citations: 6
Abstract

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)

FAPESP's process: 10/09651-6 - Synthesis and Tranfection Studies of Site-Targeted Nanocarriers of Genes
Grantee:Isadora Pfeifer Dalla Picola
Support Opportunities: Scholarships in Brazil - Doctorate