Synthesis of photoactivable Pt(IV) prodrug loaded on NaYF4 based upconversion nanoparticles functionalized with 2-deoxy-D-glucose and its evaluation for targeted cancer therapy

Abstract

Nano-formulation based on Tm, Yb doped NaYF₄ upconversion nanoparticles (UCNPs) functionalized with 2-deoxy-D-glucose have been synthesized to load the photoactivable Pt(IV) prodrug, cis-[PtI₂(NH₃)₂(OCOCH₂CH₂COOH)₂]. The Pt(IV) prodrug has been synthesized by oxidation of cis-[PtI₂(NH₃)₂] to [PtI₂(OH)₂(NH₃)₂] and its further treatment with succinic anhydride. It is loaded through ester bond formation between the carboxyl groups of Pt(IV) prodrug with hydroxyl groups of 2-deoxy-D-glucose (2-DG) coated on UCNPs. The cytotoxicity of formulation after exposing to 385 nm UV light and in absence of light is evaluated against MCF-7 cell lines by MTT assay. The results have revealed enhanced cytotoxicity of UV exposed nano-formulation. Additionally, the clonogenic assay has exhibited the decrease in plating efficiency as inferred from decreased surviving fraction around 20% only for UV activated formulation as compared to formulation in dark, as well as merely Pt(IV) prodrug. These results are indicative that more internalization of the formulation inside the cancer cells was achieved due to the presence of 2-DG rendering more efficiency to kill cancer cells.