Dioctadecyldimethylammonium:Monoolein Nanocarriers for Efficient in Vitro Gene Silencing

Autor(es)

Norberto Oliveira, Ana Cristina ^{[1, 2]} ; Martens, Thomas Frans ^{[3, 4]} ; Raemdonck, Koen ^[3] ; Adati, Renata Danielle ^[5] ; Feitosa, Eloi ^[5] ; Botelho, Claudia ^[6] ; Gomes, Andreia Castro ^[1] ; Braeckmans, Kevin ^{[3, 4]} ; Dias Real Oliveira, Maria Elisabete Cunha ^[2]

Afiliação do(s) autor(es)

^[1] Univ Minho, Dept Biol, CBMA Ctr Mol & Environm Biol, P-4710057 Braga - Portugal

^[2] Univ Minho, Dept Phys, CFUM Ctr Phys, P-4710057 Braga - Portugal

^[3] Univ Ghent, Fac Pharm, Lab Gen Biochem & Phys Pharm, B-9000 Ghent - Belgium

^[4] Univ Ghent, Ctr Nano & Biophoton, B-9000 Ghent - Belgium

^[5] Sao Paulo State Univ, Phys Dept IBILCE, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[6] Univ Minho, Inst Biotechnol & Bioengn, Ctr Biol Engn, P-4710057 Braga - Portugal

• Tipo de documento: Artigo Científico
• Fonte: ACS APPLIED MATERIALS & INTERFACES; v. 6, n. 9, p. 6977-6989, MAY 14 2014.
• Citações Web of Science: 19

Resumo

This study describes a novel liposomal formulation for siRNA delivery, based on the mixture of the neutral lipid mono olein (MO) and cationic lipids of the dioctadecyldimethylammonium (DODA) family. The cationic lipids dioctadecyldimethylammonium bromide (DODAB) and chloride (DODAC) were compared in order to identify which one will most efficiently induce gene silencing. MO has a fluidizing effect on DODAC and DODAB liposomes, although it was more homogeneously distributed in DODAC bilayers. All MO-based liposomal formulations were able to efficiently encapsulate siRNA. Stable lipoplexes of small size (100-160 nm) with a positive surface charge (>+45 mV) were formed. A more uniform MO incorporation in DODAC:MO may explain an increase of the fusogenic potential of these liposomes. The siRNA-lipoplexes were readily internalized by human nonsmall cell lung carcinoma (H1299) cells, in an energy dependent process. DODAB:MO nanocarriers showed a higher internalization efficiency in comparison to DODAC:MO lipoplexes, and were also more efficient in promoting gene silencing. MO had a similar gene silencing ability as the commonly used helper lipid 1,2-dioleyl-3-phosphatidylethanolamine (DOPE), but with much lower cytotoxicity. Taking in consideration all the results presented, DODAB:MO liposomes are the most promising tested formulation for systemic siRNA delivery. (AU)

• Processo FAPESP: 11/03566-0 - Estudos de sistemas auto-organizados de brometo de dialquildimetilamônio (DnDAB) em solução aquosa e interfaces líquidas e sólidas
• Beneficiário: Eloi da Silva Feitosa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/07414-0 - Estudo da interação entre polímeros hidrossolúveis e lipídios catiônicos em solução vesicular e em filmes moleculares como modelos de sistemas biomiméticos
• Beneficiário: Renata Danielle Adati
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado