Anti-Tumor and Anti-Angiogenic Effects of Metronomic Use of Zolendronic Acid Encapsulated in APRPG-modified PEGylated Liposomes

Zoledronic acid (ZOL) represents a 3rd generation bisphosphonate that has been reported to possess anti-tumor activity. However, its use as a chemotherapeutic drug is hindered by its short plasma half-life and rapid accumulation in bone. Therefore, the current study demonstrates the anti-angiogenic efficacy of metronomic administration of ZOL encapsulated in APRPG-modified PEGylated liposomes (APRPG-PEG-LP-ZOL), specifically in targeting vascular endothelial growth factor receptor-1 (VEGFR-1) that is known to be involved in tumor neovascularization. APRPG-PEG-LP-ZOL was synthesized using the thin-film hydration method. In vivo experiments on PC3 tumor-bearing mice were done to investigate the anti-tumor activity of metronomic APRPG-PEG-LP-ZOL administration From our results, metronomic APRPG-PEG-LP-ZOL appears to restrict tumor growth more effectively than the conventional regimen. Decreased microvessel density (MVD) confirms the anti-tumor and anti-angiogenic activity of APRPG-PEG-LP-ZOL in vivo. Our results indicate that APRPG-PEG-LP-ZOL is a rational chemotherapeutic option for cancer patients.