LAUSR

Biomaterials folded into nanoparticles (NPs) can be utilized as targeted drug delivery systems for cancer therapy. NPs may provide a vehicle for the anticancer drug lonidamine (LND), which inhibits glycolysis but was suspended from use at clinical trial stage due to hepatotoxicity attribute to poor solubility and pharmacokinetic properties. NPs prepared by self-assembly of the anionic polypeptide poly gamma glutamic acid (-PGA) with a designed amphiphilic and positively charged β-sheet peptide (designated as mPoP-NPs) enabled delivery of LND to the mitochondria in cell cultures. In this study, we demonstrate that LND-mPoP-NPs effective drug concentrations can be increased to reach therapeutically relevant concentrations. The self-assembled NPs solution was subjected to snap-freezing and lyophilization and the resultant powder was re-dissolved in a tenth of the original volume. NP size, as well as their ability to target the proximity of the mitochondria of breast cancer cells were both maintained in this new formulation, C-LND-mPoP-NPs. Furthermore, C-LND-mPoP-NPs exhibited 40% better cytotoxicity, compared to the LND-mPoP-NPs and led to tumor growth inhibition with no adverse side effects, upon intravenous administration in a xenograft breast cancer murine model.