A novel anti-angiogenic radio/photo sensitizer for prostate cancer imaging and therapy: 89Zr-Pt@TiO2-SPHINX, synthesis and in vitro evaluation

Prostate cancer is the most common malignancy and leading cause of cancer deaths in men. Thus, the development of novel strategies for performing combined prostate cancer imaging and therapy methods is crucial and could have a significant impact on patient care. This current study aimed to design a multimodality nanoconjugate to be used for both PET and optical imaging and as a therapeutic radio/photo sensitizer and anti-angiogenesis agent. Initial characterization of this novel nanoconjugate was performed via HPLC, FTIR, TEM and DLS analyses. Pt@TiO₂-SPHINX was further evaluated using fluorometric and radiochromatographic methods. Cytotoxicity, cell uptake and internalization were also investigated as well as therapy with photodynamic/radio therapy combinations. Both nanoparticles and nanoconjugates were robustly synthesized according to literature methods. Radiochemistry and cell culture assays showed high ⁸⁹Zr radiolabeling efficiency with sufficient stability for studies at later time points. Pt@TiO₂-SPHINX was shown to target prostate cancer cells (PC3 and LNCaP), and was non-toxic to normal prostate cells (RWPE-1). This finding was supported by the WST-8 assay and AFM images. The uptake of the compound in prostate cancer cells is significantly higher than prostate normal cells and according to ELISA results, Pt@TiO₂-SPHINX can increase anti-angiogenic VEGFA_165b. Additionally, Pt@TiO₂-SPHINX dramatically decreased the cell viability of prostate cancer cells when photodynamic and radio therapy were performed at the same time. In vitro results are promising for future studies of Pt@TiO₂-SPHINX as a PET imaging agent and anti-angiogenic radio sensitizer.