| Autor: |
de Oliveira FA; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil. fernando.giacomelli@ufabc.edu.br., Albuquerque LJC; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil. fernando.giacomelli@ufabc.edu.br., Nascimento-Sales M; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil. fernando.giacomelli@ufabc.edu.br., Christoffolete MA; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil. fernando.giacomelli@ufabc.edu.br., Bellettini IC; Departamento de Ciências Exatas e Educação, Universidade Federal de Santa Catarina, Blumenau, Brazil., Giacomelli FC; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil. fernando.giacomelli@ufabc.edu.br. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of materials chemistry. B [J Mater Chem B] 2023 May 24; Vol. 11 (20), pp. 4556-4571. Date of Electronic Publication: 2023 May 24. |
| DOI: |
10.1039/d3tb00477e |
| Abstrakt: |
Polyethyleneimine (PEI) derivatives substituted by lactose, succinic acid or alkyl domains were evaluated as nonviral gene delivery vectors towards balancing gene transfection and cytotoxicity. The investigations were focused on pDNA transfection into arising retinal pigment epithelia (ARPE-19) and human hepatocellular carcinoma (HepG2) cell lines. The first mentioned cell line was chosen as motivated by the non-negligible number of ocular disorders linked to gene aberrations, whereas the second one is a cell line overexpressing the asialoglycoprotein receptor (ASGP-R), which can bind to galactose residues. The presence of short alkyl domains (C 4 and C 6 ), and particularly the succinylation of the PEI chains, improved the biological outputs of the gene vectors. The presence of hydrophobic units possibly enhances lytic activity, whereas the incorporation of succinic acid slightly reduces polymer-DNA interaction strength, thereby enabling more efficient intracellular unpacking and cargo release. Succinylation is also supposed to decrease cytotoxicity and avoid protein adsorption to the polyplexes. The presence of long carbon chains (for instance, C 12 ) nevertheless, results in higher levels of cytotoxicity and respective lower transfection rates. The sugar-decorated polyplexes are overall less cytotoxic, but the presence of lactose moieties also leads to larger polyplexes and notably weak polymer-DNA binding, which compromise the transfection efficiency. Yet, along with the presence of short lytic alkyl domains, the double-substitution of PEI synergistically boosts gene transfection probably due to the uptake of higher DNA and polymer amounts without cell damage. Overall, the experimental data suggest that ocular and hepatic gene therapies may be potentialized by fine-tuning the hydrophobic-to-hydrophilic balance, and succinic acid is a favorable motif for the modification of PEI. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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