Oligo(p-phenylenevinylene) Derivative-Incorporated and Enzyme-Responsive Hybrid Hydrogel for Tumor Cell-Specific Imaging and Activatable Photodynamic Therapy

Tumor-cell targeted and subcellular organelles-specific photosensitizer is imperative for high-efficiency photodynamic therapy (PDT). Herein, we designed and synthesized a new conjugated oligomer, oligo(p-phenylenevinylene-co-benzothiazole) (OPVBT), which could be used as photosensitizer to generate reactive oxygen species (ROS) upon light illumination. Advantageously, OPVBT was found to specifically accumulate in mitochondria, which is beneficial for effective subcellular organelles-targeted PDT. A biocompatible and biodegradable hydrogel was constructed based on Michael-type addition between cysteine-terminated matrix metalloproteinase (MMP)-cleavable oligopeptides and 4-arm vinyl sulfone-terminated poly(ethylene glycol) (PEG-VS). By functionalizing hydrogel with OPVBT and cell adhesion peptide motif RGD, cell attachment and spreading on the hydrogel were easily realized. More importantly, because of the MMP-sensitivity of the hydrogel, tumor cells could be specifically lighted up by OPVBT liberated from the hydrogel and the growth of tumor cells are further restrained by ROS generated from OPVBT upon light illumination. The hybrid hydrogel provides a new platform for tumor-specific imaging and killing, which shows good potential for constructing targeted PDT system with reduced side effects.