In Situ Fabrication of Intelligent Photothermal Indocyanine Green–Alginate Hydrogel for Localized Tumor Ablation

Simplifying synthesis and administration process, improving photothermal agents’ accumulation in tumors, and ensuring excellent biocompatibility and biodegradability are keys to promoting the clinical application of photothermal therapy. However, current photothermal agents have great difficulties in meeting the requirements of clinic drugs from synthesis to administration. Herein, we reported the in situ formation of a Ca2+/Mg2+ stimuli-responsive ICG–alginate hydrogel in vivo for localized tumor photothermal therapy. An ICG–alginate hydrogel can form by the simple introduction of Ca2+/Mg2+ into ICG–alginate solution in vitro, and the widely distributed divalent cations in organization in vivo enabled the in situ fabrication of the ICG–alginate hydrogel without the leakage of any agents by simple injection of ICG–alginate solution into the body of mice. The as-prepared ICG–alginate hydrogel not only owns good photothermal therapy efficacy and excellent biocompatibility but also exhibits strong ICG fixation ability, greatly benefiting the high photothermal agents’ accumulation and minimizing the potential side effects induced by the diffusion of ICG to surrounding tissues. The in situ-fabricated ICG–alginate hydrogel was applied successfully in highly efficient PTT in vivo without obvious side effects. Besides, the precursor of the hydrogel, ICG and alginate, can be stored in a stable solid form, and only simple mixing and noninvasive injection are needed to achieve PTT in vivo. The proposed in situ gelation strategy using biocompatible components lays down a simple and mild way for the fabrication of high-performance PTT agents with the superiors in the aspects of synthesis, storage, transportation, and clinic administration.