Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
Molecular Imaging Center, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage, Chiba, 263-8555, Japan.
J Control Release. 2014 Jan 28;174:63-71. doi: 10.1016/j.jconrel.2013.10.038. Epub 2013 Nov 6.
Organic-inorganic hybrid nanoparticles with calcium phosphate (CaP) core and PEGylated shell were developed to incorporate magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) for noninvasive diagnosis of solid tumors. A two-step preparation method was applied to elaborate hybrid nanoparticles with a z-average hydrodynamic diameter about 80nm, neutral surface ξ-potential and high colloidal stability in physiological environments by self-assembly of poly(ethylene glycol)-b-poly(aspartic acid) block copolymer, Gd-DTPA, and CaP in aqueous solution, followed with hydrothermal treatment. Incorporation into the hybrid nanoparticles allowed Gd-DTPA to show significant enhanced retention ratio in blood circulation, leading to high accumulation in tumor positions due to enhanced permeability and retention (EPR) effect. Moreover, Gd-DTPA revealed above 6 times increase of relaxivity in the nanoparticle system compared to free form, and eventually, selective and elevated contrast enhancements in the tumor positions were observed. These results indicate the high potential of Gd-DTPA-loaded PEGylated CaP nanoparticles as a novel contrast agent for noninvasive cancer diagnosis.
采用两步法制备了具有 80nm 左右的 Z-均水力直径、中性表面ξ-电势和高胶体稳定性的有机-无机杂化纳米粒子，其方法是通过在水溶液中自组装聚乙二醇-b-聚天冬氨酸嵌段共聚物、Gd-DTPA 和 CaP，然后进行水热处理。Gd-DTPA 掺入杂化纳米粒子中，使 Gd-DTPA 在血液循环中的保留率显著提高，由于增强的通透性和保留（EPR）效应，导致在肿瘤部位的高聚集。此外，与游离形式相比，Gd-DTPA 在纳米粒子体系中的弛豫率增加了 6 倍以上，最终观察到肿瘤部位的选择性和升高的对比度增强。这些结果表明，载有 Gd-DTPA 的聚乙二醇化 CaP 纳米粒子作为一种新型的非侵入性癌症诊断造影剂具有很高的潜力。
