Physicochemical characterization and targeting performance of triphenylphosphonium nano-polyplexes

Faria, Rúben; Albuquerque, T.G.; Neves, Ana R.; Bhatt, Himanshu; Biswas, Swati; Cardoso, Ana M.; Lima, Maria C. Pedroso de; Jurado, Amália S.; Costa, Diana

doi:10.1016/j.molliq.2020.113873

Cited by 14 publications

(17 citation statements)

References 62 publications

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“…The plasmid pCAG-GFP-ND1 (5.4 kbp) was developed by our research group through the cloning of the mitochondrial NADH dehydrogenase 1 protein-encoded gene (mtND1) in Escherichia coli. The full description of gene cloning and plasmid production are described elsewhere [19].…”

Section: Methodsmentioning

confidence: 99%

“…Peptide/pND1 complexes were formed at different N/P ratios. The calculation of the N/P ratio is defined as the molar relation of amine groups in the peptide, which represent the positive charges, to phosphate groups in the pND1, which represent the negative charges, considering the mass per charge ratio of pND1 (330 g/mol, relative to one phosphate group) [19].…”

Section: Formulation Of Peptide/pnd1mentioning

confidence: 99%

“…In the last decade, there has been a crescendo of interest in the development of suitable nano-delivery systems to carry genetic content into the proximity of mitochondria and ensure its long-term expression, a strategy to deal with diseases related to mtDNA mutations [19,20,[40][41][42][43][44]. In this work, peptide/pND1 complexes have been developed aiming to target mitochondria and deliver pND1 plasmid into this organelle, as the first step for efficient mitochondrial gene expression.…”

Section: Pnd1 Complexation Capacitymentioning

confidence: 99%

“…The therapeutic approaches to treat mtDNA diseases have been largely ineffective, as they focus on alleviation of the symptoms. In this sense, mitochondrial gene therapy can be seen as a valuable and powerful tool to deal with these disorders, as it fights the disease at its source [18][19][20]. The direct and efficient transfection of mitochondria, with regard to replacing mutated mitochondrial genes, requires a suitable delivery system.…”

Section: Introductionmentioning

confidence: 99%

“…In the last decades, considerable advances have been made in the conception of nucleic acid-based delivery systems to overcome the major drawbacks of payload delivery to eukaryotic cells, namely, cellular uptake/internalization, endosomal escape, targeting a specific subcellular compartment, and ultimately, the induction of therapeutic action [19,[21][22][23][24]. In line with this aim, micelles, polymers, lipid-and peptide-based nanoparticles are among the most studied systems for gene release [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

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Development of Peptide-Based Nanoparticles for Mitochondrial Plasmid DNA Delivery

et al. 2021

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A mitochondrion is a cellular organelle able to produce cellular energy in the form of adenosine triphosphate (ATP). As in the nucleus, mitochondria contain their own genome: the mitochondrial DNA (mtDNA). This genome is particularly susceptible to mutations that are at the basis of a multitude of disorders, especially those affecting the heart, the central nervous system and muscles. Conventional clinical practice applied to mitochondrial diseases is very limited and ineffective; a clear need for innovative therapies is demonstrated. Gene therapy seems to be a promising approach. The use of mitochondrial DNA as a therapeutic, optimized by peptide-based complexes with mitochondrial targeting, can be seen as a powerful tool in the reestablishment of normal mitochondrial function. In line with this requirement, in this work and for the first time, a mitochondrial-targeting sequence (MTS) has been incorporated into previously researched peptides, to confer on them a targeting ability. These peptides were then considered to complex a plasmid DNA (pDNA) which contains the mitochondrial gene ND1 (mitochondrially encoded NADH dehydrogenase 1 protein), aiming at the formation of peptide-based nanoparticles. Currently, the ND1 plasmid is one of the most advanced bioengineered vectors for conducting research on mitochondrial gene expression. The formed complexes were characterized in terms of pDNA complexation capacity, morphology, size, surface charge and cytotoxic profile. These data revealed that the developed carriers possess suitable properties for pDNA delivery. Furthermore, in vitro studies illustrated the mitochondrial targeting ability of the novel peptide/pDNA complexes. A comparison between the different complexes revealed the most promising ones that complex pDNA and target mitochondria. This may contribute to the optimization of peptide-based non-viral systems to target mitochondria, instigating progress in mitochondrial gene therapy.

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Section: Methodsmentioning

confidence: 99%

Section: Formulation Of Peptide/pnd1mentioning

confidence: 99%