Fe³⁺-Induced Synchronous Formation of Composite Hydrogels for Effective Synergistic Tumor Therapy in NIR-I/II Biowindows

Alginate-Ca²⁺ hydrogel has been used to immobilize photothermal materials as well as chemotherapy drugs at lesion sites to prevent their entry into the bloodstream. However, the alginate-Ca²⁺ gelation mechanism may result in hardening of the blood vessels because of Ca²⁺ migration to the lesion site. In this study, a unique and facile one-pot formation of chemotherapeutic (doxorubicin, DOX) and polypyrrole-containing alginate hydrogel was designed by introducing Fe³⁺, which can synchronously induce the polymerization of pyrrole and gelatinization of alginate, into the DOX/pyrrole/alginate solution. The formed composite hydrogel was endowed with superior photothermal conversion properties in both the NIR-I (650–950 nm) and NIR-II (1000–1700 nm) biowindows and light-to-heat conversion efficiency higher than 50%, which enabled effective tumor hyperthermia treatment. Besides, near-infrared (NIR) irradiation could be used as a remote controller to trigger the DOX-release because of the heat generation, thus achieving continuous and on-demand tumor chemotherapy. The composite polymer hydrogels exhibited favorable hemo-, cyto-, and histocompatibility, as well as simple and cost-effective preparation and good clinical prospects.