Effective cytocompatible nanovectors based on serine-derived gemini surfactants and monoolein for small interfering RNA delivery

JOURNAL OF COLLOID AND INTERFACE SCIENCE

卷:584

Article

Costa, Catarina^1,2,3  Oliveira, Isabel S.¹  Silva, Joao P. N.¹  Silva, Sandra G.⁴  Botelho, Claudia^2,5  do Vale, M. Luisa C.⁴  Oliveira, Maria Elisabete C. D. Real³  Gomes, Andreia C.²  Marques, Eduardo F.¹ 

[1] Univ Porto, Fac Ciencias, Dept Quim & Bioquim, CIQUP, Rua Campo Alegre S-N, P-4169007 Porto, Portugal

[2] Univ Minho, Dept Biol, CBMA Ctr Biol Mol & Ambiental, Campus Gualtar, P-4710057 Braga, Portugal

[3] Univ Minho, Dept Fis, CF UM UP, Campus Gualtar, P-4710057 Braga, Portugal

[4] Univ Porto, Fac Ciencias, Dept Quim & Bioquim, LAQV REQUIMTE, Rua Campo Alegre S-N, P-4169007 Porto, Portugal

[5] Univ Minho, Dept Engn Biol, CEB Ctr Engn Biol, Campus Gualtar, P-4710057 Braga, Portugal

关键词: Gemini surfactant;    Serine;    siRNA-delivery;    Lipoplex properties;    Monoolein helper lipid;    Transfection efficiency;   

DOI  :  10.1016/j.jcis.2020.09.077

来源: Elsevier

【 摘 要 】

Non-viral gene therapy based on gene silencing with small interfering RNA (siRNA) has attracted great interest over recent years. Among various types of cationic complexation agents, amino acid-based surfactants have been recently explored for nucleic acid delivery due to their low toxicity and high biocompatibility. Monoolein (MO), in turn, has been used as helper lipid in liposomal systems due to its ability to form inverted nonbilayer structures that enhance fusogenicity, thus contributing to higher transfection efficiency. In this work, we focused on the development of nanovectors for siRNA delivery based on three gemini amino acid-based surfactants derived from serine - (12Ser)(2)N12, amine derivative; (12Ser)(2)COO12, ester derivative; and (12Ser)(2)CON12, amide derivative - individually combined with MO as helper lipid. The inclusion of MO in the cationic surfactant system influences the morphology and size of the mixed aggregates. Furthermore, the gemini surfactant:MO systems showed the ability to efficiently complex siRNA, forming stable lipoplexes, in some cases clearly depending on the MO content, without inducing significant levels of cytotoxicity. High levels of gene silencing were achieved in comparison with a commercially available standard indicating that these gemini:MO systems are promising candidates as lipofection vectors for RNA interference (RNAi)-based therapies. (C) 2020 Elsevier Inc. All rights reserved.

【 授权许可】

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