The influence of nanoparticles` coatings on drug delivery to mitochondria

Noa Harduf ¹ Ifat Cohen-Erez ^1,2 Hanna Rapaport ^1,2

¹Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel
²Ilse Katz Institute for Nanoscale Science and Technology (Iki), Ben-Gurion University of the Negev, Beer Sheva, Israel

Mitochondria play critical role in many vital cellular processes. Hence mitochondria dysfunction is implicated in numerous diseases. Various drugs have been developed to treat mitochondria. Such drugs should cross several cell membrane and other intracellular barriers before reaching the mitochondria.

We have previously developed a nanoparticles (NPs) based drug-delivery system to mitochondria. These NPs are based on co-assembly of the anionic polypeptide poly-ɤ-glutamic acid (ɤ-PGA) and a designed amphiphilic and cationic β-sheet peptide (PFK). PFK that was formulated as the NPs coating was found to facilitate their co-localization within the proximity of the mitochondria.

In this study we hypothesized that NPs coating can be modulated to influence their intracellular delivery and cytotoxicity. To test this hypothesis, we created NPs with PFK and examined new coating variations using similar to PFK peptides.

NPs coated by the new peptides, loaded with and such without the chemotherapeutic drug Lonidamine, were characterized for their physical properties, cellular uptake and effect on cells viability. Results indicate that indeed variations in peptide coatings influence the NPs` cellular localization and cytotoxicity.