Nanoparticles for the delivery of zoledronic acid to prostate cancer cells: A comparative analysis through time lapse video-microscopy technique

Abstract

Time-lapse live cell imaging is a powerful tool for studying the responses of cells to drugs. Zoledronic acid (ZOL) is the most potent aminobiphosphonate able to induce cell growth inhibition at very low concentrations. The lack of clear evidence of ZOL-induced anti-cancer effects is likely due to its unfavorable pharmacokinetic profile. The use of nanotechnology-based formulations allows overcoming these limitations in ZOL pharmaco-distribution. Recently, stealth liposomes (LIPOs) and new self-assembly PEGylated nanoparticles (NPs) encapsulating ZOL were developed. Both the delivery systems showed promising anticancer activity in vitro and in vivo.

In this work, we investigated the cytostatic effect of these novel formulations (LIPOs and NPs) compared with free ZOL on 2 different prostate cancer cell lines, PC 3 and DU 145 and on prostate epithelial primary cells EPN using time lapse video-microscopy (TLVM). In PC3 cells, free ZOL showed a significant anti-proliferative effect but this effect was lower than that induced by LIPOs and NPs encapsulating ZOL; moreover, LIPO-ZOL was more potent in inducing growth inhibition than NP-ZOL. On the other hand, LIPO-ZOL slightly enhanced the free ZOL activity on growth inhibition of DU 145, while the anti-proliferative effect of NP-ZOL was not statistically relevant. These novel formulations did not induce anti-proliferative effects on EPN cells. Finally, we evaluated cytotoxic effects on DU145 where, LIPO-ZOL induced the highest cytotoxicity compared with NP-ZOL and free ZOL. In conclusion, ZOL can be transformed in a powerful anticancer agent, if administered with nanotechnology-based formulations without damaging the healthy tissues.

Keywords:

• cell biology
• cell toxicity
• drug delivery
• motility
• nanotechnology
• nanotoxicology
• prostate cancer
• self-assembly PEGylated nanoparticles
• stealth liposomes
• time lapse video-microscopy
• zoledronic acid

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

MC was supported from the Italian Ministry of Education, University and Research (MIUR) with a project (FIRB-ACCORDI DI PROGRAMMA 2011) entitled “Application of High-Throughput Technology Platforms for the Characterization of New Biomarkers and Molecular Targets in Nanovectors for the Diagnosis and Treatment of Human Cancer” Moreover, MC was also partially supported by from Regione Campania in a project entitled “Laboratori Pubblici Hauteville.”