Department of Chemistry, University of California, Berkeley, California 94720-1460, United States.
Mol Pharm. 2013 Jan 7;10(1):69-76. doi: 10.1021/mp3003754. Epub 2012 Dec 26.
The fields of nanotechnology and medicine have merged in the development of new imaging and drug delivery agents based on nanoparticle platforms. As one example, a mutant of bacteriophage MS2 can be differentially modified on the exterior and interior surfaces for the concurrent display of targeting functionalities and payloads, respectively. In order to realize their potential for use in in vivo applications, the biodistribution and circulation properties of this class of agents must first be investigated. A means of modulating and potentially improving the characteristics of nanoparticle agents is the appendage of PEG chains. Both MS2 and MS2-PEG capsids possessing interior DOTA chelators were labeled with (64)Cu and injected intravenously into mice possessing tumor xenografts. Dynamic imaging of the agents was performed using PET-CT on a single animal per sample, and the biodistribution at the terminal time point (24 h) was assessed by gamma counting of the organs ex vivo for 3 animals per agent. Compared to other viral capsids of similar size, the MS2 agents showed longer circulation times. Both MS2 and MS2-PEG bacteriophage behaved similarly, although the latter agent showed significantly less uptake in the spleen. This effect may be attributed to the ability of the PEG chains to mask the capsid charge. Although the tumor uptake of the agents may result from the enhanced permeation and retention (EPR) effect, selective tumor imaging may be achieved in the future by using exterior targeting groups.
纳米技术和医学领域已经融合在一起,开发出了基于纳米颗粒平台的新型成像和药物输送剂。例如,噬菌体 MS2 的突变体可以在外部和内部表面上进行不同的修饰,分别用于靶向功能和有效载荷的同时显示。为了实现它们在体内应用中的潜力,必须首先研究这类试剂的生物分布和循环特性。一种调节和潜在改善纳米颗粒试剂特性的方法是添加 PEG 链。具有内部 DOTA 螯合剂的 MS2 和 MS2-PEG 衣壳都用 (64)Cu 标记,并静脉注射到具有肿瘤异种移植物的小鼠体内。使用 PET-CT 在每个样本中对每个动物进行一次动态成像,并通过对每个试剂的 3 个器官进行体外伽马计数来评估终末时间点(24 小时)的生物分布。与其他类似大小的病毒衣壳相比,MS2 试剂表现出更长的循环时间。MS2 和 MS2-PEG 噬菌体的行为相似,尽管后者在脾脏中的摄取量明显较少。这种效果可能归因于 PEG 链能够掩盖衣壳电荷。尽管这些试剂的肿瘤摄取可能是由于增强的渗透和保留 (EPR) 效应所致,但未来通过使用外部靶向基团可能实现选择性肿瘤成像。