Efficacy of Chitosan-N-Arginine Chitosomes in mRNA Delivery and Cell Viability Enhancement

Autor(es)

Garcia, Bianca B. M. ; Douka, Stefania ; Mertins, Omar ; Mastrobattista, Enrico ; Han, Sang W.

• Tipo de documento: Artigo Científico
• Fonte: ACS APPLIED BIO MATERIALS; v. N/A, p. 11-pg., 2024-11-19.

Resumo

Cationic lipid-based carriers are recognized for their ability to complex with mRNA and effectively deliver the mRNA for vaccination and therapeutic purposes. However, the significant cytotoxicity of these carriers often restricts their practical application. In the present study, polymer-lipid hybrid nanoparticles, termed chitosomes, incorporating chitosan-N-arginine (CSA) with the DOTAP cationic lipid and the DOPE helper lipid, were synthesized and evaluated. The addition of CSA to the lipid formulations improved their physicochemical stability and enhanced mRNA complexation, resulting in high transfection rates in the HeLa and HEK293T cell lines. However, the transfection efficiency was low in the NIH-3T3 cell line, indicating a cell type-specific response to chitosomes. Importantly, CSA significantly reduced the cytotoxicity typically associated with DOTAP. Overall, the present study indicated that optimizing the ratio of CSA to DOTAP is crucial for developing mRNA nanocarriers to achieve high transfection efficiency and reduce cytotoxicity across different cell lines. (AU)

• Processo FAPESP: 20/06913-1 - Desenvolvimento de nanopartículas de quitossomas para modulação da inflamação e angiogênese por dual delivery: uma abordagem para a terapia gênica para isquemia de membros
• Beneficiário: Bianca Bonetto Moreno Garcia
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 22/04361-7 - Desenvolvimento de quitossomas para delivery de mRNA a células NK
• Beneficiário: Bianca Bonetto Moreno Garcia
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 23/03903-3 - Investigação do papel da ANXA1 na recuperação da isquemia de membro e desenvolvimento de terapia gênica com vetores não virais
• Beneficiário: Sang Won Han
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/00971-2 - Nano cubossoma de fase cristalina e funcionalizado com biopolímeros: desenvolvimento como carreador de fármaco e estudos in vivo em zebrafish (Danio rerio)
• Beneficiário: Omar Mertins
• Modalidade de apoio: Auxílio à Pesquisa - Regular