Rational Design of a High-Performance Quinoxalinone-Based AIE Photosensitizer for Image-Guided Photodynamic Therapy

Because light exhibits excellent spatiotemporal resolution, photodynamic therapy (PDT) is becoming a promising method for cancer treatment. However, in a single photosensitizer (PS), it remains a big challenge to achieve all key properties including effective singlet oxygen (¹O₂) production under long-wavelength laser and bright near-infrared (NIR) emission without toxicity in the dark. In addition, clinically used traditional PSs encounter quenched fluorescence and decreased ¹O₂ production because of molecular aggregation in aqueous solution. To solve the aforementioned issues, quinoxalinone CN (QCN) with effective ¹O₂ generation under long-wavelength (530 nm) laser irradiation and aggregation-induced NIR emission is rationally designed by precise optimization of the quinoxalinone scaffold. After being encapsulated by an amphiphilic polymer (DSPE-PEG), the yielded nanoparticles exhibit highly efficient ¹O₂ production and stable NIR fluorescence located at 800 nm without obvious toxicity under the dark. Both in vitro and in vivo evaluation identify that QCN would be a promising PS for image-guided PDT of tumors.