Injectable and Natural Humic Acid/Agarose Hybrid Hydrogel for Localized Light-Driven Photothermal Ablation and Chemotherapy of Cancer.

The injection of theranostic drug-laden hydrogels into subcutaneous tumors has proven to be a promising strategy to achieve precise local tumor eradication. Humic acid, a natural product of biochemical decomposition of animal and plant residues, abundantly exists in soils, peats, oceans, etc. In this study, a robust injectable thermoresponsive agarose hydrogel incorporating sodium humate (SH) and doxorubicin (DOX) was constructed as a unique agent for tumor management based on the combined chemo-photothermal therapeutic effect. SH, which strongly absorbs near-infrared (NIR) light, can efficiently convert light energy into thermal energy, induce local hyperthermia and subsequently trigger sustained drug release from the complex of the SH/DOX@hydrogel through a typical gel-sol transition, resulting in enhanced cellular uptake of therapeutic drugs. Moreover, intratumoral injection of the SH/DOX@hydrogel resulted in a simultaneous chemo-photothermal therapeutic effect against solid tumors under NIR laser irradiation, which may collectively prevent tumor recurrence. In addition, the SH/DOX@hydrogel exhibited ultralow systemic toxicity as demonstrated using an animal model. This work provides a promising attempt to develop a low-cost, light-responsive hydrogel for precise tumor therapy, which may also incorporate extra theranostic modules as an advanced platform for the treatment of cancer or other critical diseases.