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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.

In spite of widespread applications of nano-photosensitizers, poor tumor penetration and severe hypoxia in the tumor microenvironment (TME) always result in an undesirable therapeutic outcome of photodynamic therapy (PDT).