Engineering a theranostic platform for synergistic hypoxia-responsive photodynamic therapy and chemotherapy

Photodynamic therapy (PDT) has become an attractive alternative in the field of oncology therapy; however, its therapeutic efficacy is suppressed by the hypoxic tumor microenvironment within solid tumors. We engineered a theranostic molecule (DHQ-Cl-Azo) with hypoxia-responsive chemical and PDT functionalities for the cooperative treatment of solid tumors. DHQ-Cl-Azo is an innovative photosensitizer that is regulated by an intersystem crossing process. Reduction of the theranostic construct in the hypoxic tumor microenvironment led to the release of a near-infrared-emissive fluorophore and an active chemotherapeutic drug. Subsequently, during PDT, DHQ-Cl-Azo helped eliminate normoxic tumor cells in the surface layer of the tumor, and during activatable chemotherapy, it helped eliminate hypoxic tumor cells in the tumor center, thereby maximizing treatment efficacy for solid tumors in mice. Overall, this study introduced a new theranostic construct by integrating hypoxia-sensitive dual-modality therapies and fluorescence diagnosis to improve therapeutic efficacy of PDT for solid tumors.