Near infrared light-responsive heat-emitting hemoglobin hydrogels for photothermal cancer therapy

Photothermal therapy (PTT) is an effective means of treating tumors because tumor cells are sensitive to heat. Gold and carbon nanoparticles are used as efficient PTT materials. However, development of a non-toxic biodegradable PTT agent remains a challenge. Here, we developed a hemoglobin (Hb) hydrogel that exhibited excellent PTT effects in vitro and in vivo. Unlike conventional PTT agents, which are toxic and do not decompose completely in the body, the Hb hydrogel was manufactured using only two components: (i) Hb, a natural substance derived from the human body, and (ii) PEG, an FDA-approved polymer. The gelation time of the Hb hydrogels could be controlled by changing the Hb concentration. Because Hb is present at a high concentration (150 mg/ml) in the body, the Hb hydrogel decomposed and was eliminated in vivo without toxicity. The Hb hydrogel showed an excellent PTT effect in response to 808 nm near-infrared (NIR) laser irradiation and had excellent anticancer effects against A549 lung cancer cells both in vitro and in vivo. Blood hematology and blood biochemical assay results from an animal model treated with Hb hydrogel were similar to those of the control group. Importantly, toxicity was not observed based on H&E staining of major organs (heart, liver, spleen, kidneys and lung). Tumors of A549 cell-xenografted mice treated with Hb hydrogel and 808 nm NIR laser irradiation were significantly smaller than those of the control group (23.1 mm³versus 746.5 mm³, respectively). This is a first report of a biocompatible photothermal hydrogel based on hemoglobin, and our overall results suggest that Hb hydrogels are commercially-promising PTT systems that have excellent anti-cancer effects.