Executive Summary : | Photodynamic therapy (PDT) has gained interest in recent decades due to its better spatial-temporal control and non-invasive nature. However, it faces challenges such as cancer targetability, photostability of the sensitizer, singlet oxygen generation quantum yield, and hypoxia. In situ oxygen production inside tumor cells using manganese dioxide (MnO2) has gained attention. Recently, it has been hypothesized that non-canonical DNA structures, particularly DNA G-quadruplex (G4), are involved in various biological functions. stabilizing G4 structures via small molecules in telomeres can prevent the activity of the enzyme telomerase and trigger apoptosis in cancer cells, making G4 targeting an innovative and efficient approach to developing targeted therapeutic probes. This proposal aims to develop organic probes that can stabilize DNA G4 structures and induce anti-cancer action as a combined effect of G4 stabilization and PDT activity. The project also aims to develop a nanocomposite by conjugating the organic probes with MnO2 nanostructures. This strategy is expected to generate promising synergistic therapeutic effects by increasing oxygen concentration at the microenvironment of cancer cells by the catalytic action of MnO2 on the splitting of intracellular H2O2. The successful implementation of this project will demonstrate possibilities and encourage researchers to design and develop PDT drugs based on the concept for clinical application. |