Chlorella-gold nanorods hydrogels generating photosynthesis-derived oxygen and mild heat for the treatment of hypoxic breast cancer

Hypoxic tumors are rarely cured because their low oxygen environment restricts the cytotoxicity of many chemotherapeutics by blocking the production of intracellular reactive oxygen species. Inspired by the highly efficient production of oxygen as a waste product of chlorella photosynthesis, we developed an in situ rapidly gelling BSA-PEG–based hydrogel depot system that contains chlorella and gold nanorods, namely Chlorella AuNRs BSA-Gel. The entrapped chlorella in our gel efficiently generated a high level of oxygen and oxygenated hemoglobin via photosynthesis in response to 660-nm light in vitro and in vivo, respectively. The incorporated gold nanorods showed excellent performance in precisely increasing the surrounding temperature to 41–42 °C responding to 808-nm near-infrared laser, which presumably played a supporting role in expanding the tumor vasculature and thereby facilitating the delivery of doxorubicin and oxygen to hypoxic tumors of mice. Our results showed that a combined therapy of Chlorella AuNRs BSA-Gel plus Dox followed by irradiation at 660 nm and 808 nm significantly abolished 4 T1 breast cancer cell-xenografted tumors of BALB/C mice. We believe that our oxygen-generating and mild heat-emitting hydrogel should be considered to be a valid prototype of a local depot system for treatment of hypoxic tumors.