Integration of Activation by Hypoxia and Inhibition Resistance of Tumor cells to Apoptosis for Precise and Augmented Photodynamic Therapy

Photodynamic therapy (PDT) uses photosensitizers to convert oxygen (O-2) to reactive oxygen species (ROS) under irradiation to induce DNA damage and kill cancer cells. However, the effect of PDT is usually alleviated by apoptosis resistance mechanism of tumor living cells. MTH1 enzyme is known to be such an apoptosis-resistance enzyme which is over expressed as a scavenger to repair the damaged DNA. In this work, a hypoxia-activated nanosystem FTPA, which can be degraded to release the encapsulated PDT photosensitizer 4-DCF-MPYM and an inhibitor TH588 is proposed. The inhibitor TH588 can inhibit the DNA repair process by reducing the activity of MTH1 enzyme, and achieve the purpose of amplifying the therapeutic effect of PDT. This work demonstrates that a precise and augmented tumor PDT is achieved by integration of hypoxia-activation and inhibition resistance of tumor cells to apoptosis.

Automated summary

Photodynamic therapy (PDT) utilizes photosensitizers to generate reactive oxygen species (ROS) from oxygen (O-2) under irradiation, leading to DNA damage and cancer cell death. However, apoptosis resistance mechanisms in tumor cells reduce the effectiveness of PDT. This study introduces a hypoxia-activated nanosystem FTPA, which releases the encapsulated PDT photosensitizer 4-DCF-MPYM and an inhibitor TH588. The inhibitor TH588 inhibits DNA repair by reducing the activity of MTH1 enzyme, thus enhancing the therapeutic effect of PDT. The integration of hypoxia activation and apoptosis resistance inhibition achieves precise and augmented tumor PDT.