Journal
JOURNAL OF MOLECULAR LIQUIDS
Volume 309, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.molliq.2020.113157
Keywords
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Funding
- Fundo Social Europeu e Programa Operacional Potencial Humano [IF/01459/2015]
- FCT [FCOMP-01-0124-FEDER-041068, UID/Multi/00709/2019, SFRH/BD/148393/2019, SFRH/BD/148406/2019]
- FCT (FEDER funds through the POCI - COMPETE 2020 - Operational Program Competitiveness and Internationalisation in Axis I -Strengthening research, technological development and innovation) [POCI-01-0145-FEDER-007491]
- Programa Operacional do Centro, Centro 2020 through ICON Project (Interdisciplinary Challenges on Neurodegeneration) [CENTRO-01-0145-FEDER-000013]
- [POCI-01-0145-FEDER-022122]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/148393/2019, SFRH/BD/148406/2019] Funding Source: FCT
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Polymer/peptide/plasmid DNA (pDNA) based ternary systems were developed by combining the great condensing ability of both polyethylenimine (PEI) and cell-penetrating peptides (RALA or TAT). This approach leads to the formation of lower sized vectors displaying positive charges and a high pDNA complexation ability, at low nitrogen to phosphate groups ratio. Compared to the binary polymer/pDNA or peptide/pDNA complexes, higher amounts of PEI or peptides are required to condense the pDNA and conceive formulations with similar properties. Moreover, the polymer/peptide/pDNA nanopartides are able of pDNA release when the intracellular environment was mimicked. Taking advantage of the favourable characteristics, for cellular uptake and gene delivery exhibited by ternary systems, in vitro studies were performed on cancer cells. The obtained results revealed the capacity of the developed carriers for cell internalization and pDNA localization within or in dose proximity to the nucleus. In line with this, gene expression was detected and the produced protein levels were quantified. and showed to be significantly higher when compared to binary pDNA based carriers. The PEI/peptide/pDNA ternary systems offer remarkable potential for the conceptual design and formation of advanced bio-functional vectors towards the most demanding biomedical applications. (C) 2020 Elsevier B.V. All rights reserved.
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