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

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Author(s):
Garcia, Bianca B. M. ; Douka, Stefania ; Mertins, Omar ; Mastrobattista, Enrico ; Han, Sang W.
Total Authors: 5
Document type: Journal article
Source: ACS APPLIED BIO MATERIALS; v. N/A, p. 11-pg., 2024-11-19.
Abstract

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)

FAPESP's process: 20/06913-1 - Development of chitosomes' nanoparticles for modulation of inflammation and angiogenesis by dual delivery: an approach to gene therapy for limb ischemia
Grantee:Bianca Bonetto Moreno Garcia
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 22/04361-7 - Development of chitosomes for mRNA Delivery to NK cells
Grantee:Bianca Bonetto Moreno Garcia
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 23/03903-3 - Investigation of the role of ANXA1 in limb ischemia recovery and development of gene therapy with non-viral vectors
Grantee:Sang Won Han
Support Opportunities: Regular Research Grants
FAPESP's process: 21/00971-2 - Crystalline-phase nano cubosome functionalized with biopolymers: development as a drug carrier and in vivo studies in zebrafish (Danio rerio)
Grantee:Omar Mertins
Support Opportunities: Regular Research Grants