(642e) Aminoglycoside-Derived Liposomes for Drug Delivery

Breast cancer is one of the leading cancers in women, and is responsible for an estimated 50,000 deaths every year in the US. Triple-negative breast cancer (TNBC) is diagnosed in 15-30% of all breast cancer cases, and dvelopment targeted therapeutics are challenging due to lack of estrogen, progesterone, and HER2 receptors in this disease. Aminoglycosides contain multiple sugar groups with with amines and hydroxyls, and have been investigated as antibiotics in the clinic. Aminoglycoside-derived lipid-containing polymers were formulated into nanoparticles (liposomes) for encapsulation and delivery of mitoxantrone, an FDA-approved DNA damaging drug, to different cancer cells. Five different liposomes were synthesized, formulated and characterized for their size, surface charge, and stability over time. The efficacy of liposomal mitoxantrone for ablation of TNBC, bladder, and prostate cancer cells was evaluated both as a single-agent treatment and in combination with TRAIL (Tumor Necrosis Factor-apha Related Apoptosis-Inducing Ligand), which is a protein that has been shown to selectively kill cancer cells compared to normal cells. In addition the combination of liposomal mitoxantrone with PARP (poly ADP ribose polymerase enzyme) inhibitors was also evaluated in cancer cells. Liposomal mitoxantrone demonstrated 6-10 fold higher efficacy for ablation of cancer cells compared to unencapsulated drug in vitro. In vivo biodistribution and efficacy of liposomal mitoxontrone is being studied using TNBC tumor-bearing mice.