- 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 (γ-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 the peptide (LND-mPoP-NPs). In this study, we improved the drug capacity of the LND-mPoP-NPs in addition to lowering non-specific toxicity associated with the drug deficient mPoP-NPs. LND concentrations in LND-mPoP-NPs were increased (h-LND-mPoP-NPs) and the peptide coating concentration was decreased. The new h-LND-mPoP-NPs formulation shows the ability to carry the drug to the proximity of the mitochondria despite the NP's negative zeta potential.