Aptamer-functionalized nanoscale metal-organic frameworks for targeted photodynamic therapy

Abstract

Photodynamic therapy (PDT) has been applied in clinical cancer treatment. Here we report an aptamer-functionalized nanoscale metal-organic framework for targeted PDT. Our nanosystem can be easily prepared and successfully used for targeted PDT with a significantly enhanced therapeutic efficacy <i>in vitro</i> and <i>in vivo</i>. <b>Methods:</b> By combining the strong binding ability between phosphate-terminated aptamers and Zr-based nanoscale metal-organic frameworks (Zr-NMOFs) and the intercalation of photosensitizer TMPyP4 within the G-quadruplex DNA structure, TMPyP4-G4-aptamer-NMOFs were prepared. The characteristics and photodynamic performance of TMPyP4-G4-aptamer-NMOFs were examined after preparation. Then, we studied their stability, specific recognition ability, and phototoxicity <i>in vitro</i>. For <i>in vivo</i> experiments, the nanosystem was intratumorally injected into a HeLa subcutaneous xenograft tumor mouse model. After irradiation on day 0, mice were further injected with the nanosystem on day 5 and were again subjected to laser irradiation for 30 min. Tumor volumes and body weights of all mice were measured by caliper every 2 days after the treatment. <b>Results:</b> The nanosystem induced 90% cell death of targeted cells. In contrast, the control cells maintained about 40% cell viability at the same concentration of nanosystem. For the <i>in vivo</i> experiments, the nanosystem-treated group maintained more than 76% inhibition within the entire experimental period. <b>Conclusion:</b> We have demonstrated that our smart TMPyP4-G4-sgc8-NMOFs nanosystem can be used for targeted cancer therapy with high efficiency.