Effectiveness of drug treatment is highly dependent on delivering the therapeutics to the target organ and cells and even to specific intracellular organelles. In several human disorders mitochondria are relevant cellular targets for drug delivery. A challenging problem in the development of drug therapy to treat mitochondrial dysfunction is related to controlling the insertion and distribution of the drug in the cell.
Nanoparticles (NPs) may improve cellular targeted therapy due to their potential ability to deliver payloads directly to specific organelles within cells, while simultaneously enhancing stability and controlling pharmacokinetics.
In this study we developed NPs based on spontaneous co-assembly of γ-PGA, a natural polypeptide and a designed peptide for intracellular chemotherapeutic delivery into the mitochondria. We demonstrated the formation of various NPs in a range of sizes and surface charges. The secondary structure of the peptide has been determined by Circular Dichroism. The NPs were found to be spherical based on AFM measurements with diameter in the nanometric size range that were also confirmed by DLS and SAXS. NPs were loaded with chemotherapeutics such as dequalinium and lonidamine. Moreover, mito-targeted NPs that were developed using peptide coatings, were found by confocal microscopy to localize in the mitochondria of osteosarcoma saos2 cells.
ifatc@bgu.ac.il
