Negatively Charged Polypeptide-Peptide Nanoparticles Showing Efficient Drug Delivery to the Mitochondria

Polymeric nanoparticles (NPs) represent an effective platform for drug delivery systems, albeit with various limitations including low drug loading capacity, cytotoxicity and specificity. NPs composed of the negatively charged Polypeptide, poly gamma glutamic acid (g-PGA) and a designed amphiphilic and cationic β-sheet Peptide (denoted PoP-NPs) loaded with the drug lonidamine (LND), denoted LND-PoP-NPs were previously used in our lab to successfully target the mitochondria when coated with peptide and exhibiting positive zeta potential (LND-mPoP-NPs).¹ In this study, we improved the drug capacity of the LND-mPoP-NPs in addition to lowering nonspecific toxicity associated with the NPs carrier formulation, i.e. the drug deficient, mitochondria targeting NPs. In the new NPs LND concentrations was 3 times higher compare to LND-mPoP-NPs, and the peptide coating concentration was decreased to a level that the NPs zeta potential remained negative. This new formulation, h-LND-mPoP-NPs, shows improved cytotoxic effect supported by the NPs` ability to carry the high dose drug to the proximity of the mitochondria apparently with no toxic side effects that are linked to positively charged NP carriers.²

1. Cohen-Erez I, Rapaport H. Coassemblies of the anionic polypeptide γ-PGA and cationic β-sheet peptides for drug delivery to mitochondria. Biomacromolecules. 2015. 16 (12), 3827-3835.
2. Cohen-Erez I, Rapaport H. Negatively charged polypeptide-peptide nanoparticles showing efficient drug delivery to the mitochondria. Submitted. 2017.