Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice
Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice
复制标题
Zr-89标记黑色素纳米粒子在铁超载小鼠体内的药代动力学研究
DOI：
10.1016/j.nucmedbio.2016.05.014
复制
发表时间：
2016-09-01
影响因子：
3.1
通讯作者：
Yang, Min
中科院分区：
文献类型：
--
作者：
Zhang, Pengjun;Yue, Yuanyuan;Yang, Min
黑色素是一种存在于许多生物体中的天然生物色素，已被发现具有多种功能。黑色素的一个重要特性是其对金属离子的强烈螯合能力，其可能被开发为用于铁过载治疗的铁螯合剂。本研究制备了超小水溶性黑色素纳米粒，并首次评价了其在铁负荷小鼠体内的药代动力学，为治疗铁负荷提供科学依据。为了研究MP的循环时间和生物分布，用Zr-89标记MP，Zr-89是一种长半衰期（78.4 h）的正电子发射金属，其适合于标记纳米颗粒和大的生物活性分子。MP直接与Zr-89在pH 5下螯合，导致89.6%的非衰变校正产率和大于98%的放射化学纯度。比活性至少为190 MBq/tanol。Zr-89-MP在人血浆和PBS中可稳定至少48 h。Zr-89-MP在铁超载小鼠中的半衰期约为15.70 +/- 1.74 h。生物分布研究和MicroPET成像显示，Zr-89-MP主要蓄积在肝脏和脾脏，这是铁过载的靶器官。结果表明，黑色素纳米颗粒有希望用于进一步的铁过载治疗。(C)2016 Elsevier Inc. All rights reserved.
Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin nanoparticle (MP) and firstly evaluate the pharmacokinetics of MP in iron-overload mice to provide scientific basis for treating iron-overload. To study the circulation time and biodistribution, MP was labeled with Zr-89, a long half-life (78.4 h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with Zr-89 directly at pH 5, resulting in non-decay-corrected yield of 89.6% and a radiochemical purity of more than 98%. The specific activity was at least190 MBq/tanol. The Zr-89-MP was stable in human plasma and PBS for at least 48 h. The half-life of Zr-89-MP was about 15.70 +/- 1.74 h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that Zr-89-MP mainly accumulated in liver and spleen, which are the target organ of iron-overload. The results indicate that the melanin nanoparticle is promising for further iron overload therapy. (C) 2016 Elsevier Inc. All rights reserved.