Photothermal therapy (PTT) that utilizes
hyperthermia to ablate
cancer cells is a promising approach for
cancer therapy, while the generated high temperature may lead to damage of surrounding normal tissues and
inflammation. We herein report the construction of
glucose oxidase (GOx)-loaded
hydrogels with a pH-sensitive photothermal conversion property for combinational
cancer therapy at mild-temperature. The
hydrogels (defined as CAG) were formed via coordination of
alginate solution containing pH-sensitive charge-transfer nanoparticles (CTNs) as the second near-infrared (NIR-II) photothermal agents and GOx. In the
tumor sites, GOx was gradually released from CAG to consume
glucose for
tumor starvation and aggravate acidity in tumor microenvironment that could turn on the NIR-II photothermal conversion property of CTNs. Meanwhile, the released GOx could suppress the expression of
heat shock proteins to enable mild NIR-II PTT under 1,064 nm
laser irradiation. As such, CAG mediated a combinational action of mild NIR-II PTT and
starvation therapy, not only greatly inhibiting the growth of subcutaneously implanted
tumors in a
breast cancer murine model, but also completely preventing lung
metastasis. This study thus provides an
enzyme loaded
hydrogel platform with a pH-sensitive photothermal effect for mild-temperature-mediated combinational
cancer therapy.