A multi-stimuli responsive alginate nanogel for anticancer chemo-photodynamic therapy

Stimuli-responsive nanosystems enable highly effective targeting and therapeutic functions, including chemotherapy and photodynamic therapy (PDT). Traditional PDT alone cannot effectively eradicate the tumor burden; combined with chemotherapy, this combination presents a powerful treatment modality to modulate the tumor microenvironment (TME). Herein, we report a multi-stimulus responsive alginate nanogel that responds to the change in pH and redox potential in the TME. We coupled oxidized alginate with 4-mercapto phenylboronic acid and pheophorbide-A (a hydrophobic photosensitizer) and conjugated with adipic acid dihydrazide to design the nanogels. Further, we encapsulated doxorubicin, a cytotoxic agent, in the nanogel to enable chemotherapy. The alginate nanogel exhibited the pH-sensitive release of both pheophorbide-Aand doxorubicin and simultaneously reduced the redox potential that enhanced PDT by increasing reactive oxygen species production. Our results demonstrate that the multi-stimuli responsive alginate nanogel enhances toxicity in breast cancer and melanoma.