Cheng Fong-Yu, Chiou Yuan-Yow, Hung Shih-Yuan, Lin Tsun-Mei, Wang Hao-Kuang, Lin Chi-Wei, Liou Hung-Hsiang, Chang Min-Yu, Wang Hsi-Hao, Lee Yi-Che
Department of Chemistry, Chinese Culture University, Taipei, Taiwan.
Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan.
Int J Nanomedicine. 2021 Mar 11;16:2137-2146. doi: 10.2147/IJN.S291001. eCollection 2021.
Vitamin D3 is useful for the treatment of peritoneal dialysis (PD)-related peritoneal damage, but its side effects, such as hypercalcemia and vascular calcification, limit its applicability. Thus, we developed vitamin D-loaded magnetic nanoparticles (MNPs) and determined their therapeutic efficacy and side effects in vivo.
Alginate-modified MNPs were combined with 1α, 25 (OH)D to generate vitamin D-loaded nanoparticles. The particles were conjugated with an antibody against peritoneum-glycoprotein M6A (GPM6A). The particles' ability to target the peritoneum was examined following intraperitoneal administration to mice and by monitoring their bio-distribution. We also established a PD animal model to determine the therapeutic and side effects of vitamin D-loaded MNPs in vivo.
Vitamin D-loaded MNPs targeted the peritoneum better than vitamin D3, and had the same therapeutic effect as vitamin D3 in ameliorating peritoneal fibrosis and functional deterioration in a PD animal model. Most importantly, the particles reduced the side effects of vitamin D3, such as hypercalcemia and body weight loss, in mice.
Vitamin D-loaded MNPs could be an ideal future therapeutic option to treat PD-related peritoneal damage.
维生素D3对治疗腹膜透析(PD)相关的腹膜损伤有用,但其副作用,如高钙血症和血管钙化,限制了其适用性。因此,我们开发了负载维生素D的磁性纳米颗粒(MNPs),并确定了它们在体内的治疗效果和副作用。
将海藻酸盐修饰的MNPs与1α,25(OH)D结合以生成负载维生素D的纳米颗粒。这些颗粒与抗腹膜糖蛋白M6A(GPM6A)的抗体偶联。在向小鼠腹腔内给药后,通过监测其生物分布来检查颗粒靶向腹膜的能力。我们还建立了一个PD动物模型,以确定负载维生素D的MNPs在体内的治疗效果和副作用。
负载维生素D的MNPs比维生素D3更好地靶向腹膜,并且在改善PD动物模型中的腹膜纤维化和功能恶化方面与维生素D3具有相同的治疗效果。最重要的是,这些颗粒减少了维生素D3在小鼠中的副作用,如高钙血症和体重减轻。
负载维生素D的MNPs可能是未来治疗PD相关腹膜损伤的理想治疗选择。