Ma Li Leo, Feldman Marc D, Tam Jasmine M, Paranjape Amit S, Cheruku Kiran K, Larson Timothy A, Tam Justina O, Ingram Davis R, Paramita Vidia, Villard Joseph W, Jenkins James T, Wang Tianyi, Clarke Geoffrey D, Asmis Reto, Sokolov Konstantin, Chandrasekar Bysani, Milner Thomas E, Johnston Keith P
Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, USA.
ACS Nano. 2009 Sep 22;3(9):2686-96. doi: 10.1021/nn900440e.
The ability of 20-50 nm nanoparticles to target and modulate the biology of specific types of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. Herein we report approximately 30 nm stable uniformly sized near-infrared (NIR) active, superparamagnetic nanoclusters formed by kinetically controlled self-assembly of gold-coated iron oxide nanoparticles. The controlled assembly of nanocomposite particles into clusters with small primary particle spacings produces collective responses of the electrons that shift the absorbance into the NIR region. The nanoclusters of approximately 70 iron oxide primary particles with thin gold coatings display intense NIR (700-850 nm) absorbance with a cross section of approximately 10(-14) m(2). Because of the thin gold shells with an average thickness of only 2 nm, the r(2) spin-spin magnetic relaxivity is 219 mM(-1) s(-1), an order of magnitude larger than observed for typical iron oxide particles with thicker gold shells. Despite only 12% by weight polymeric stabilizer, the particle size and NIR absorbance change very little in deionized water over 8 months. High uptake of the nanoclusters by macrophages is facilitated by the dextran coating, producing intense NIR contrast in dark field and hyperspectral microscopy, both in cell culture and an in vivo rabbit model of atherosclerosis. Small nanoclusters with optical, magnetic, and therapeutic functionality, designed by assembly of nanoparticle building blocks, offer broad opportunities for targeted cellular imaging, therapy, and combined imaging and therapy.
20 - 50纳米的纳米颗粒靶向并调节特定类型细胞生物学特性的能力,将推动癌症和动脉粥样硬化细胞成像与治疗领域取得重大进展。一个关键挑战是要将极高程度的靶向、成像和治疗功能加载到小而稳定的颗粒中。在此,我们报告了通过动力学控制金包覆氧化铁纳米颗粒的自组装形成的尺寸约为30纳米、大小均匀、近红外(NIR)活性的超顺磁性纳米团簇。将纳米复合颗粒可控组装成初级颗粒间距小的团簇,会产生电子的集体响应,使吸光度转移到近红外区域。由约70个带有薄金涂层的氧化铁初级颗粒组成的纳米团簇,在700 - 850纳米处显示出强烈的近红外吸光度,截面约为10(-14)平方米。由于金壳平均厚度仅为2纳米,其r(2)自旋 - 自旋磁弛豫率为219 mM(-1) s(-1),比具有较厚金壳的典型氧化铁颗粒观察到的值大一个数量级。尽管聚合物稳定剂的重量仅为12%,但在去离子水中8个月内颗粒大小和近红外吸光度变化很小。葡聚糖涂层促进了巨噬细胞对纳米团簇的高摄取,在细胞培养和动脉粥样硬化的体内兔模型中,在暗场和高光谱显微镜下都产生了强烈的近红外对比度。通过纳米颗粒构建块的组装设计的具有光学、磁性和治疗功能的小纳米团簇,为靶向细胞成像、治疗以及联合成像与治疗提供了广阔的机会。