Evaluation of the efficacy of carbon nanotubes for delivering peptides into mitochondria

Abstract

Mitochondrial (mt) diseases are devastating neurodegenerative pathologies due tomutations in nuclear or mt genes. Among mtDNA pathogenic mutations, more than one half have been identified in transfer RNA (tRNA) genes. These are responsible for a wide range of pathologies including myopathies, encephalopathies, cardiomyopathies and deafness for which no effective treatment is available at present. Therefore, new strategies to suppress their damaging effects are required to envisage therapeutic approaches for these diseases. Here we report data for carbon nanotube (CNT) derivatives showing that the conjugates bearing a specific peptide sequence are able to target the mitochondria in yeast and human monocyte cells while the control derivative without the peptide diffuses into the cytoplasm. Moreover the compounds do not affect cellular viability and cytotoxicity both in vitro and in vivo. Toxicity of the constructs is also assessed on the simple pluricellular model Caenorhabditis elegans

Derivatized Carbon Nanotubes for Gene Therapy in Mammalian and Plant Cells

“…Ficociello et al [39] have successively carried out 1,3-dipolar cycloaddition reaction in the presence of protected amino acids and paraformaldehyde to form MWCNTs based drug delivery system. Mild oxidation followed by secondary covalent functionalization can tune the CNTs to carry a genetic load, targeting ligand, and a fluorophore for multi-modal applications.…”

“…Ficociello et al . have successively carried out 1,3‐dipolar cycloaddition reaction in the presence of protected amino acids and paraformaldehyde to form MWCNTs based drug delivery system.…”

Designing multimodal carbon nanotubes by covalent multi-functionalization

“…Alternatively, the double functionalized CNTs have been prepared by two successive 1,3-dipolar cycloaddition of azomethine ylides. 47 The first cycloaddition was performed in the presence of a phthalimide-protected amino acid derivative and paraformaldehyde, followed by a second reaction using a Boc-protected amino acid compound. The CNTs were sequentially derivatized with a specific peptide sequence able to target the mitochondria and with FITC.…”

Carbon nanotubes functionalized with α-aminoisobutyric acid-containing peptide increase gene delivery efficiency in plant mitochondria

“…Genetic engineering of plants remains one of the most promising and economical approaches to scaling food and energy production for the world population and addressing limitations in food and energy production associated with climate change [1][2][3]. Biological applications using singlewalled carbon nanotubes (SWNTs) have emerged as potential delivery tools for plants due to their wide biocompatibility and outstanding delivery efficiency [4][5][6][7][8][9]. SWNTs have been shown to be capable of crossing plant cell walls and membranes, likely due to their unique physical properties, including their high aspect ratio, surface area, and stiffness [7,10].…”