Injectable hydrogel platform with biodegradable Dawson-type polyoxometalate and R848 for combinational photothermal-immunotherapy of cancer

Photothermal therapy (PTT) is a powerful strategy for cancer treatment with minimal invasiveness but still limited by lack of long-term efficacy against tumor recurrence and toxicity concerns about the slow biodegradability of the PTT agents. Herein, an injectable hydrogel platform (R848/POM@GG) of gellan gum co-loaded with Dawson-type {P2Mo18} polyoxometalate (POM) and Toll-like receptors agonist resiquimod (R848) is developed for combinational photothermal-immunotherapy of cancer. The POM-based gellan gum hydrogel (POM@GG) exhibits high photothermal conversion efficiency (63.1%) at a safe power density of 0.3 W cm-2 and good photostability during five cycles. By further incorporation of R848, the obtained R848/POM@GG exerts synergetic photothermal-immunotherapy on solid tumors, giving a high tumor inhibition rate of 99.3% and negligible lung metastases in the breast cancer mice models. A strong antitumor immune system with significantly elevated TNF-α, IL-2, and IL-6 levels is activated by R848. Additionally, the POM clusters gradually degrade to nontoxic molybdate in the physiological environment. Overall, the injectable hydrogel platform of R848/POM@GG has great translational potential for localized antitumor treatments.