Virginia Commonwealth University, Center for Molecular Imaging, P.O. Box 980031, Richmond, VA, USA.
Virginia Commonwealth University, Center for Molecular Imaging, P.O. Box 980031, Richmond, VA, USA.
Nanomedicine. 2018 Jun;14(4):1429-1440. doi: 10.1016/j.nano.2018.04.002. Epub 2018 Apr 8.
Cerium oxide nanoparticles (CONPs) have unique surface chemistry allowing catalyst-like antioxidant properties, and are being investigated for several disease indications in medicine. Studies have utilized surface modified CONPs toward this application, but have been lacking in comprehensive biodistribution and pharmacokinetic data and a direct comparison to uncoated CONPs. We developed an enhanced single-pot synthesis of several coated CONPs and an efficient intrinsic core labeling of CONPs with the clinical PET isotope, zirconium-89, allowing detailed PET imaging and ex vivo biodistribution. All coated [Zr]-CONPs showed benefit in terms of biodistribution compared to uncoated [Zr]-CONPs, while retaining the intrinsic antioxidant properties. Among these, poly(acrylic acid) coated CONPs demonstrated excellent candidacy for clinical implementation due to their enhanced renal clearance and low reticuloendothelial system uptake. This work also demonstrates the value of intrinsic core labeling and PET imaging for evaluation of nanoparticle constructs to better inform future studies towards clinical use.
氧化铈纳米颗粒（CONPs）具有独特的表面化学性质，具有类催化剂抗氧化特性，目前正在医学领域的多种疾病适应症中进行研究。研究已经将表面修饰的 CONPs 用于该应用，但缺乏全面的生物分布和药代动力学数据，以及与未涂层 CONPs 的直接比较。我们开发了一种增强的单一合成方法，可合成几种涂层 CONPs，并可有效地将 CONPs 用临床 PET 同位素锆-89 进行内在核心标记，从而实现详细的 PET 成像和离体生物分布。与未涂层的 [Zr]-CONPs 相比，所有涂层的 [Zr]-CONPs 在生物分布方面都表现出了优势，同时保留了内在的抗氧化特性。在这些涂层中，由于其增强的肾脏清除率和低网状内皮系统摄取率，聚丙烯酸涂层 CONPs 表现出极好的临床应用候选性。这项工作还证明了内在核心标记和 PET 成像对于评估纳米颗粒构建体的价值，以便更好地为未来的临床应用研究提供信息。
