Purpose: PTT is an effective means of treating tumor because tumor cells are sensitive to heat. However, the development of a non-toxic biodegradable PTT agent remains a challenge. Here we have developed a hemoglobin hydrogel that exhibit excellent photothermal effects in vivo. Unlike conventional PTT preparations, which are toxic and not well decomposed in the body, hemoglobin hydrogels are manufactured using hemoglobin, substances of the body, and PEG, an FDA-approved polymer. Because hemoglobin is a protein that exists at a high concentration (150 mg / ml) in the body, the hemoglobin hydrogel is decomposed and eliminated in vivo without any toxicity.
Methods: Hemoglobin (300 mg) was dissolved in 2 ml of 10 mM PBS buffer (pH 7.4) containing 2-iminothiolane (3mg) and then reacted by stirring for 1 h. The molecular weight of hemoglobin reacted with 2-IT (HB-SH) was analyzed by Matrix-Assisted Laser Desorption and Ionization - Time of Flight Mass Spectrometry (MALDI-TOF MS). 100 μl of various HB-SH concentration (60, 90, 120, 150 mg) was reacted with 50 μl of 4-arm PEG-MAL. The final concentrations of the prepared hemoglobin are 60, 80, 100 and 120 mg/ml, respectively.
Results: This hydrogel showed excellent photothermal effect in response to 808 nm NIR laser irradiation and excellent anticancer effects in vitro and in vivo when A549 cells were used. When visualized with a photothermal camera, the temperature of hemoglobin hydrogel increased from 60 ° C at 10 minutes after NIR laser irradiation. The hematology markers and indicators for liver and kidneys of animal model injected three times the therapeutic dose of hydrogel showed similar results to the control group.
Conclusion: In summary, we fabricated biodegradable hemoglobin hydrogel. These hemoglobin hydrogels showed excellent phototherapeutic effect in response to NIR laser irradiation. We believe that this hydrogel can be developed as a commercially available PTT system with no toxicity and excellent anti-cancer effects.
Changkyu Lee– Post-doc, Sungkyunkwan University
Sanghyun Park– Sungkyunkwan University
Bohyung Seo– Sungkyunkwan University
Sung Soo Kim– Graduate Student, SungKyunKwan University, Suwon-si, Kyonggi-do
Yu Seok Youn– Professor, Sungkyunkwan University