Green and Kilogram-Scale Synthesis of Fe Hydrogel for Photothermal Therapy of Tumors in Vivo

Photothermal agents with good biocompatibility, high tumor accumulation efficiency, large-scale production ability, and low cost are crucial for potential photothermal treatment in clinic. Herein, we proposed a green and highly efficient strategy to fabricate a kilogram-scale alginate-Ca²⁺-Fe powder hydrogel (ALG-Ca²⁺-Fe) by turning commercial Fe powder into hydrogel for enhanced photothermal therapy. The ALG-Ca²⁺-Fe was formed by simply dispersing commercial Fe powder into the preformed alginate-Ca²⁺ hydrogel in a green and energy-/time-saving way. The hydrogel exhibited the advantages of ultrahigh loading capacity of Fe powder (>100 mg mL^–1), excellent large-scale production capacity (>1 kg in lab synthesis), low cost (<1.7 $/kg), and good injectability. More importantly, large size and hydrophobicity endowed Fe powder with excellent tumor retention effect and minimal diffusion to surrounding tissues, greatly benefiting improving treatment efficiency and reducing side effects. In vivo and in vitro studies both proved that the large-scale produced ALG-Ca²⁺-Fe can be used for highly efficient and biosafe tumor treatment in vivo by simple noninvasive injection. The developed ALG-Ca²⁺-Fe with multiple superiors opens up a novel green way to develop efficient and safe photothermal therapeutic agents with great clinic transformation potential.