Nucleic acid delivery to retinal cells using lipopeptides as a potential tool towards ocular gene therapies.

Autor: Albuquerque LJC; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil., de Oliveira FA; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil., Christoffolete MA; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil., Nascimento-Sales M; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil., Berger S; Department of Pharmacy and Center for NanoScience (CeNs), Ludwig-Maximilians-Universität, Munich, Germany., Wagner E; Department of Pharmacy and Center for NanoScience (CeNs), Ludwig-Maximilians-Universität, Munich, Germany., Lächelt U; Department of Pharmacy and Center for NanoScience (CeNs), Ludwig-Maximilians-Universität, Munich, Germany; Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria., Giacomelli FC; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil. Electronic address: fernando.giacomelli@ufabc.edu.br.
Jazyk: angličtina
Zdroj: Journal of colloid and interface science [J Colloid Interface Sci] 2024 Feb; Vol. 655, pp. 346-356. Date of Electronic Publication: 2023 Nov 04.
DOI: 10.1016/j.jcis.2023.11.003
Abstrakt: We evaluated the use of lipopeptides capable to bind to nucleic acids towards plasmid DNA (pDNA) delivery. The investigations were particularly focused on arising retinal pigment epithelial cells (ARPE-19) as motivated by the considerable number of ocular disorders linked to gene aberrations. The lipopeptides comprised the artificial oligoamino acid succinyl-tetraethylene pentamine (Stp) as well as incorporated lysines, histidines, cysteines, fatty acids, and tyrosine trimers. Regardless of the structural differences, the lipopeptides demonstrated to efficiently condense pDNA at nitrogen-to-phosphate molar ratio (N/P) ≥ 6. Spheric nanoparticles were observed by cryo-TEM and dynamic light scattering determined hydrodynamic sizes ranging from 50 to 130 nm. The biological assays evidenced highly efficient pDNA delivery with a lower degree of cytotoxicity compared to the well-known transfecting agent linear polyethylenimine (LPEI). Although more efficient than LPEI, cysteine-containing carriers were demonstrated to be less efficient than the other counterparts possibly due to exceeding polyplex stabilization via disulfide cross links, which could hamper pDNA unpacking at the target site. Therefore, clearly a balance between complex stability and cargo release should be taken into account to optimize the transfection efficiency of the non-viral vectors. The gene transfer activity in ARPE-19 cells suggests the applicability of this kind of carrier for ocular treatments based on retinal gene delivery.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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