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Nanomechanics of Fosbretabulin A4 polymeric nanoparticles in liver cancer cells

Liver cancer remains one of the most dreaded malignancies worldwide. Multidrug resistance, toxicity, adverse drug reactions and poor bioavailability are among the major barriers for successful anticancer therapeutics. Hence, there is an urgent need for nanotechnology-based new therapies for this aggressive disease to be explored. The purpose of this study was to develop a chemotherapeutic drug Fosbretabulin A4 (Ftub A4) encapsulated in pegylated polymeric poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (100-200 nm) for microtubule targeted delivery to human liver cancer cells. The effect of cell-particle molecular interactions was also evaluated. Physicochemical properties of these nanoparticles were characterized using dynamic light scattering, zeta-potential, transmission electron microscopy and scanning electron microscopy. The cellular internalization of nanoparticles was observed by confocal laser scanning microscopy and transmission electron microscopy. Potent antiproliferative and apoptotic activities of Ftub A4 nanoparticle treatment in comparison to the free drug were observed in liver cancer cells. In conclusion, Ftub A4 delivery modality greatly sensitized liver cancer cells as well as perturbed the microtubule assembly leading to enhanced antitumour effects. The results indicated that the nanoformulation has strong therapeutic potential in metastatic liver malignancies.