Enhancing electron transfer of a semiconducting polymer for type I photodynamic and photothermal synergistic therapy

Tumor hypoxia is responsible for the reduced therapeutic efficacy of type II photodynamic therapy (PDT) because of the dependence of cellular oxygen during ¹O₂ generation. Type I PDT may be a better strategy to overcome the disadvantages of hypoxia for enhanced theranostics. Herein, a new semiconducting polymer PDPP was synthesized and encapsulated with hydrophilic PEG-PDPA to enhance the electron transfer for type I PDT. PDPP NPs show a high superoxide radical generation ability with DHR123 as a probe. In vitro MTT assay indicates PDPP NPs with considerably high phototoxicity on human cervical cancer cells (HeLa) with a low half-maximal inhibitory concentration (IC₅₀) of 6.1 μg/ml. Furthermore, an in vivo study demonstrates that PDPP NPs can lead to complete tumor suppression with the help of laser, compared with the control and dark groups. The biosafety is confirmed by the H&E analysis of the normal tissues (the heart, liver, spleen, lungs, and kidney). The results provide a strategy to design nanosystems for type I PDT and PTT synergistic therapy.