Gold-Loaded Polymeric Micelles

描述（由申请人提供）：最近，人们对使用金纳米颗粒（GNP）作为X射线计算机断层扫描（CT）成像应用的造影剂越来越感兴趣。这在很大程度上是因为每单位重量的金提供的X射线衰减几乎是碘的三倍，并且GNP通常表现出比三碘苯加合物显著更长的循环时间。这些有益的性质使得GNP在动物模型中既可用作血池又可用作靶向成像剂。虽然结果很有希望，但GNP从肝脏中消除的时间很长。例如，已经发现，在静脉注射40 nm GNP后，从第1天到第6个月，肝脏中的金含量仅下降9%。这些发现可能是临床翻译的主要障碍。全身清除率可以用1.9nm GNP改善，因为它们足够小以进行肾小球过滤;然而，这些较小的GNP具有较短的循环时间，并且具有较小的横截面积和较短的X射线衰减路径长度。因此，预期它们对于CT血管造影术和靶向成像研究不太有利，其中能够衰减X射线的GNP的数量受到靶部位细胞表面受体数量的限制。该提案的总体目标是开发可有效排泄的可生物降解GNP，同时仍具有有利于CT血管造影和靶向成像研究的几何尺寸。本提案的具体目的是（1）合成并表征具有各种物理和化学性质的载金聚合物胶束（GPMs）;（2）评价GPMs的生物分布、循环时间和保留;以及（3）表征抗HER 2抗体偶联GPMs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.