Kumar Yadav Sanjeev, Kumar Srivastava Anup, Dev Atul, Kaundal Babita, Roy Choudhury Subhasree, Karmakar Surajit
Nanotechnology. 2017 Aug 18;28(36):365102. doi: 10.1088/1361-6528/aa7c76.
Melatonin (MEL) has promising medicinal value as an anticancer agent in a variety of malignancies, but there are difficulties in achieving a therapeutic dose due to its short half-life, low bioavailability, poor solubility and extensive first-pass metabolism. In this study chitosan/tripolyphosphate (TPP) nanoparticles were prepared by an ionic gelation method to overcome the therapeutic challenges of melatonin and to improve its anticancer efficacy. Characterization of the melatonin-loaded chitosan (MEL-CS) nanoformulation was performed using transmission and scanning electron microscopies, dynamic light scattering, Fourier transform infrared spectroscopy, Raman spectroscopy and x-ray diffraction. In vitro release, cellular uptake and efficacy studies were tested for their enhanced anticancer potential in human U87MG glioblastoma cells. Confocal studies revealed higher cellular uptake of MEL-CS nanoparticles and enhanced anticancer efficacy in human malignant glioblastoma cancer cells than in healthy non-malignant human HEK293T cells in mono- and co-culture models. Our study has shown for the first time that MEL-CS nanocomposites are therapeutically more effective as compared to free MEL at inducing functional anticancer efficacy in the human brain tumour U87MG cell line.
褪黑素（MEL）作为一种抗癌剂在多种恶性肿瘤中具有潜在的药用价值，但由于其半衰期短、生物利用度低、溶解度差以及广泛的首过代谢，难以达到治疗剂量。在本研究中，通过离子凝胶法制备了壳聚糖/三聚磷酸钠（TPP）纳米颗粒，以克服褪黑素的治疗挑战并提高其抗癌疗效。使用透射电子显微镜、扫描电子显微镜、动态光散射、傅里叶变换红外光谱、拉曼光谱和X射线衍射对负载褪黑素的壳聚糖（MEL-CS）纳米制剂进行了表征。对体外释放、细胞摄取和功效进行了研究，以测试其在人U87MG胶质母细胞瘤细胞中增强的抗癌潜力。共聚焦研究表明，在单培养和共培养模型中，MEL-CS纳米颗粒在人恶性胶质母细胞瘤癌细胞中的细胞摄取高于健康的非恶性人HEK293T细胞，且抗癌功效增强。我们的研究首次表明，与游离MEL相比，MEL-CS纳米复合材料在诱导人脑肿瘤U87MG细胞系产生功能性抗癌功效方面具有更高的治疗效果。
