Molecularly Self-Engineered Nanoamplifier for Boosting Photodynamic Therapy via Cascade Oxygen Elevation and Lipid ROS Accumulation

Photodynamic therapy (PDT) has been extensively explored as a noninvasive cancer treatment modality. However, the dilemma of tumor hypoxia and short half-life of singlet oxygen (O-1(2)) severely restrict the therapeutic efficacy of PDT. Herein, we develop a facile three-in-one PDT nanoamplifier (AA@PPa/Hemin NPs) assembled by pyropheophorbide a (PPa), hemin, and arachidonic acid (AA). Interestingly, AA not only acts as an enabler to facilitate the assembly of PPa and hemin in the construction of ternary hybrid nanoassemblies but also acts as a lipid reactive oxygen species (ROS) amplifier for robust PDT. In tumor cells, hernia plays the role of a catalase-like catalyst that accelerates the production of oxygen (O-2) from hydrogen peroxide (H2O2), significantly alleviating tumor hypoxia. Under laser irradiation, vast amounts of O-1(2) generated by PPa trigger the peroxidation of AA to produce large amounts of cytotoxic lipid ROS, immensely amplifying the efficiency of PDT by promptly eliciting cellular oxidative stress. As expected, AA@PPa/Hemin NPs exert potent antitumor activity in a 4T1 breast-tumor-bearing BALB/c mice xenograft model. Such a cascade nanohybrid amplifier provides a novel codelivery platform for accurate and effective PDT of cancer.

Automated summary

A novel three-in-one photodynamic therapy nanoamplifier is developed to address the challenges of tumor hypoxia and short half-life of singlet oxygen. The nanoamplifier facilitates the assembly of materials and amplifies the photodynamic therapy effect through the production of lipid reactive oxygen species. It exhibits potent antitumor activity in a mouse tumor model.