Evaluation of the potential of lycopene encapsulated polymeric nanoparticles associated with D-±-tocopheryl polyethylene glycol 1000 succinate functionalized with bevacizumab in the treatment of Prostate Cancer

Abstract

Prostate Cancer is the second Cancer with the highest mortality in Brazil, affecting mainly men in old age. The recommended treatment varies according to the tumor stage, and it is possible to choose therapies alone or in combination. Among therapies, chemotherapeutic agents are widely used; however, the tumor may show resistance causing the efflux of drugs from the cell, in addition to generating numerous side effects because it also affects healthy cells. Substances of natural origin, such as lycopene, the carotenoid responsible for the red pigmentation of tomatoes (Solanum lycopersicum), have shown antiangiogenesis and antitumor action in in vitro tests of Prostate Cancer strains. However, lycopene is highly hydrophobic and has low bioavailability, and its incorporation in drug delivery systems based on nanotechnology, such as polymeric nanoparticles associated with D-±-tocopheryl polyethylene glycol 1000 (TPGS) succinate, which has gained space in Cancer therapy, as they can encapsulate hydrophilic or hydrophobic substances, improve drug stability properties, help in the controlled release process, solubility in water, reduce toxicity, internalization and apoptosis of Cancer cells. The nanoparticles can have their surface modified by the coupling of ligands or antibodies that assist in specific binding to the target cell, such as bevacizumab, an antiangiogenesis agent, a property that is associated with the invasive process of the tumor. Thus, the present work aims to encapsulate lycopene in polymeric nanoparticles associated with TPGS and functionalize them with bevacizumab for the treatment of Prostate Cancer. The nanoparticles developed will be physicochemically characterized, evaluated for functionalization efficiency, encapsulation, lycopene release in vitro, cytotoxicity in vitro against prostate tumor cell lines (PC-3 and DU145) and in vivo antitumor activity. (AU)