Gold-Loaded Polymeric Micelles

描述(申请人提供)：最近，人们对将纳米金(GNPs)用作X射线计算机断层扫描(CT)成像应用的造影剂的兴趣与日俱增。这在很大程度上是因为黄金提供的单位重量的X射线衰减几乎是碘的三倍，而且GNPs的循环时间通常比三碘苯加合物要长得多。这些有益的特性使GNPs在动物模型中既可用作血池，又可用作靶向显像剂。尽管结果很有希望，但GNPs在肝脏中的清除时间很长。例如，研究发现，静脉注射40纳米GNPs后，从第1天到第6个月，肝脏中的金含量只下降了9%。这些发现很可能成为临床翻译的主要障碍。使用1.9 nm的GNPs可以改善全身清晰度，因为它们足够小，可以进行肾小球过滤；然而，这些较小的GNPs循环时间较短，具有较小的横截面积和较短的X射线衰减路径长度。因此，它们预计不太适用于CT血管造影术和靶向成像研究，在这些研究中，能够衰减X射线的GNP数量受到靶点细胞表面受体数量的限制。这项提议的总体目标是开发可生物降解的GNPs，该GNPs可以有效地排泄，同时仍具有有利于CT血管成像和靶向成像研究的几何尺寸。这一建议的具体目标是：(1)合成和表征具有不同物理化学性质的载金聚合物胶束(GPM)；(2)评价GPM的生物分布、循环时间和保留率；(3)表征抗HER2结合的GPM的靶向能力。

DESCRIPTION (provided by applicant): Recently, there has been growing interest in the use of gold nanoparticles (GNPs) as contrast agents for x-ray computed tomography (CT) imaging applications. This is largely because gold provides almost three times greater X-ray attenuation per unit weight than iodine and GNPs generally exhibit significantly longer circulation times than tri-iodobenzene adducts. These beneficial properties have allowed GNPs to be used as both blood pool and targeted imaging agents in animal models. Although the results have been promising, GNPs suffer from protracted elimination from the liver. For example, it has been found that there is only a 9% fall in the content of gold in the liver from day 1 to 6 months, following the intravenous injection of 40nm GNPs. These findings are likely to present a major impediment for clinical translation. Whole-body clearance can be improved with 1.9nm GNPs, since they are small enough to undergo glomerular filtration; however, these smaller GNPs have shorter circulation times and possess a smaller cross-sectional area and shorter path length for x-ray attenuation. Therefore, they are expected to be less favorable for CT angiography and targeted imaging studies, where the number of GNPs capable of attenuating x-rays is limited by the number of cell surface receptors at the target site. The overall goal of this proposal is to develop biodegradable GNPs that can be efficiently excreted, while still possessing geometric dimensions that are favorable for CT angiography and targeted imaging studies. The specific aims for this proposal are (1) Synthesize and characterize gold-loaded polymeric micelles (GPMs) with various physical and chemical properties; (2) Evaluate the biodistribution, circulation time, and retention of GPMs; and (3) Characterize the targeting capabilities of anti-HER2-affibody conjugated GPMs.