Antitumor effect of lonidamine-polypeptide-peptide nanoparticles in breast cancer models

Ifat Cohen Erez ¹ Hanna Rapaport ^1,2

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

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 coassembly of the anionic polypeptide poly gamma glutamic acid (g-PGA) and a designed amphiphilic and positively charged peptide (designated as mPoP-NPs) delivered LND to 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, these NPs exhibited 40% better cytotoxicity, relative to the non lyophilized LND-mPoP-NPs and led to tumor growth inhibition with no adverse side effects, upon intravenous administration in a xenograft breast cancer murine model.