Coomassie Bright Blue-Conjugated Human Serum Albumin Nanoparticles as a Tumor-Selective Weapon for Leukemia Therapy

Abstract

Leukemia is a group of blood cancers which seriously endangers the health of many people, especially children and adolescents. Although some drugs have been developed to treat leukemia, these drugs always have harmful side effects, which seriously affect the quality of life of patients. Therefore, the development of a special drug which damages only leukemia cells and does not harm normal cells remains a challenge. In a previous study, we developed a novel nanomedicine, Cy5.5MSA-G250, which selectively kills fast-growing tumor cells without harming normal cells. Based on our previous work, we prepared Cy5.5-HSA-G250 nanoparticles (CHGNPs) by replacing mouse serum albumin (MSA) with low immunogenic human serum albumin (HSA), and then applied this nanomaterial in leukemia treatment. Under physiological conditions, the CHGNPs exhibited good dispersion and stability, and hemolytic experiments showed that this material has excellent blood compatibility. The cell endocytosis of CHGNPs was obviously inhibited after treatment with nystatin and chlorpromazine, implying that caveolae-mediated endocytosis and clathrin-mediated endocytosis are involved in the cellular uptake of CHGNPs. Cytotoxicity and apoptosis assays revealed that the CHGNPs severely inhibited leukemia cell proliferation and induced leukemia cell apoptosis but did not affect normal cells. The selective up-regulation of tumor suppressor protein P27 and inducement of G1 arrest in leukemia cells may be the main mechanisms for CHGNPs' selective cytotoxicity. Owing to these advantages of CHGNPs, we believe that CHGNPs can be used as a potential leukemia drug for clinical treatment.