Targeted delivery of elesclomol using a magnetic mesoporous platform improves prostate cancer treatment both in vitro and in vivo

Abstract

BackgroundTo improve the anticancer properties of elesclomol (ELC), targeted theranostic nanoparticles (NPs; APT-PEG-Au-MMNPs@ELC) were designed to increase the selectivity of the drug delivery system (DDS). Materials and methodsELC was synthesized and entrapped in the open porous structure of magnetic mesoporous silica nanoparticles (MMNPs). The pore entrance of MMNPs was then blocked using gold gatekeepers. Finally, the external surfaces of the particles were grafted with functional polyethylene glycol (PEG) and EpCAM aptamer to generate biocompatible and targeted NPs. In the next step, the physicochemical properties of prepared NPs were fully evaluated and their anticancer potential was evaluated both in vitro and in vivo. ResultsThe targeted NPs were successfully synthesized with a final size diameter of 81.13 ± 7.41 nm. The results indicated a pH-dependent release pattern, which sustained for 72 h despite an initial rapid release. Upon exposure to APT-PEG-Au-MMNPs@ELC, higher cytotoxicity was observed in human prostate cancer cells (PC-3) as compared with control Chinese hamster ovary (CHO) cells, indicating higher specificity of targeted NPs against EpCAM-positive cancerous cells. Moreover, APT-PEG-Au-MMNPs@ELC could induce apoptosis in PC-3 cells. In vivo results on a PC-3 xenograft tumor model demonstrated that targeted NPs could significantly inhibit tumor growth and diminish severe side effects of ELC, compared to the free drug. ConclusionCollectively, APT-PEG-Au-MMNPs@ELC could be considered a promising theranostic platform for the targeted delivery of ELC to improve its therapeutic effects in prostate cancer.