Microfluidic Assembly of Monodisperse, Nanoparticle-Incorporated Perfluorocarbon Microbubbles for Medical Imaging and Therapy
Microfluidic Assembly of Monodisperse, Nanoparticle-Incorporated Perfluorocarbon Microbubbles for Medical Imaging and Therapy
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DOI：
10.1021/la102272d
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发表时间：
2010-09-07
期刊：
影响因子：
3.9
通讯作者：
Matsuura, Naomi
中科院分区：
文献类型：
--
作者：
Seo, Minseok;Gorelikov, Ivan;Matsuura, Naomi
新型医学成像造影剂允许使用单一试剂进行多种成像和治疗应用，可以对病变组织进行更准确的诊断和局部治疗。固体纳米颗粒 (NP)（尺寸为 5-150 nm）已成为有前途的成像和治疗剂，微米级的全氟化碳气体填充微泡 (MB) 在患者中用作血管内超声造影剂。我们提出，将小型固体纳米颗粒和较大的高度可压缩的MB模块化组合成单一试剂是获得两种截然不同的试剂所需的互补和混合特性的有效方法。这里提出了一种新策略，基于对 NP 和 MB 壳之间静电引力的基于 pH 值的受控调节，将各种医用 NP 与单分散 MB 简单而稳健地结合。使用这种简单的方法，微流体生成的、蛋白质脂质涂层的全氟丁烷MB（尺寸控制低至3μm）与二氧化硅涂层的纳米粒子结合，包括CdSe/ZnS量子点、金纳米棒、氧化铁纳米粒子和负载Gd的介孔二氧化硅纳米粒子。二氧化硅界面允许纳米粒子包含在 MB 中，而不受纳米粒子组成、形态和尺寸的影响。值得注意的是，使用低压超声可检测到稀释在盐水中的 NP 掺入 MB（NP-MB），并且单分散 MB 平台可以高通量生产，足以在体内使用（10(6) MB/秒）。各种 NP-MB 的模块化合成可以促进针对特定应用和疾病类型定制的灵活、用户定义的多功能成像和治疗剂。
New medical imaging contrast agents that permit multiple imaging and therapy applications using a single agent can result in more accurate diagnosis and local treatment of diseased tissue. Solid nanoparticles (NPs) (5-150 nm in size) have emerged as promising imaging and therapy agents, as have micrometer-scale, perfluorocarbon gas-filled microbubbles (MBs) used in patients as intravascular ultrasound contrast agents. We propose that the modular combination of small, solid NPs and larger, highly compressible MBs into a single agent is an effective way to attain the desired complementary and hybrid properties of two very different agents. Presented here is a new strategy for the simple and robust incorporation of various medical NPs with monodisperse MBs based upon the controlled pH-based regulation of the electrostatic attraction between NPs and the MB shell. Using this simple approach, microfluidic-generated, protein-lipid-coated, perfluorobutane MBs (with size control down to 3 mu m) were incorporated with silica-coated NPs, including CdSe/ZnS quantum dots, gold nanorods, iron oxide NPs, and Gd-loaded mesoporous silica NPs. The silica interface permits NP inclusion within MBs to be independent of NP composition, morphology, and size. Significantly, the NP-incorporated MBs (NP-MBs) diluted in saline were detectable using low-pressure ultrasound, and the monodisperse M B platform can be produced at high-throughput, sufficient for in vivo usage (10(6) MB/sec). The modular synthesis of a variety of NP-MBs can facilitate flexible, user-defined, multifunctional imaging and therapy agents tailored for specific applications and disease types.