Hyaluronan-fullerene/AIEgen nanogel as CD44-targeted delivery of tirapazamine for synergistic photodynamic-hypoxia activated therapy

Abstract The therapeutic effect of oxygen-concentration-dependent photodynamic therapy (PDT) can be diminished in the hypoxic environment of solid tumours, the effective solution to this problem is utilising hypoxic-activated bioreduction therapy (BRT). In this research, a biocompatible HA-C60/TPENH 2 nanogel which can specifically bind to CD44 receptor was developed for highly efficient PDT-BRT synergistic therapy. The nanogel was degradable in acidic microenvironments of tumours and facilitated the release of biological reduction prodrug tirapazamine (TPZ). Importantly, HA-C60/TPENH 2 nanogel produced reactive oxygen species and consumed oxygen content in the cell to activate TPZ, leading to higher cytotoxicity than the free TPZ did. The intracellular observation of nanogel indicated that the HA-C60/TPENH 2 nanogel was self-fluorescence for cell imaging. This study applied PDT-BRT to design smart HA-based nanogel with targeted delivery, pH response, and AIEgen feature for efficient cancer therapy.