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多功能树枝状大分子包裹的金纳米粒子用于双模 CT/MR 成像应用。

Multifunctional dendrimer-entrapped gold nanoparticles for dual mode CT/MR imaging applications.

机构信息

College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China.

出版信息

Biomaterials. 2013 Feb;34(5):1570-80. doi: 10.1016/j.biomaterials.2012.11.010. Epub 2012 Nov 28.

Abstract

We report the synthesis, characterization, and utilization of gadolium-loaded dendrimer-entrapped gold nanoparticles (Gd-Au DENPs) for dual mode computed tomography (CT)/magnetic resonance (MR) imaging applications. In this study, amine-terminated generation five poly(amidoamine) dendrimers (G5.NH₂) modified with gadolinium (Gd) chelator and polyethylene glycol (PEG) monomethyl ether were used as templates to synthesize gold nanoparticles (AuNPs). Followed by sequential chelation of Gd(III) and acetylation of the remaining dendrimer terminal amine groups, multifunctional Gd-Au DENPs were formed. The formed Gd-Au DENPs were characterized via different techniques. We show that the formed Gd-Au DENPs are colloidally stable and non-cytotoxic at an Au concentration up to 50 μM. With the coexistence of two radiodense imaging elements of AuNPs and Gd(III) within one NP system, the formed Gd-Au DENPs display both r₁ relaxivity for MR imaging mode and X-ray attenuation property for CT imaging mode, which enables CT/MR dual mode imaging of the heart, liver, kidney, and bladder of rat or mouse within a time frame of 45 min. Furthermore, in vivo biodistribution studies reveal that the Gd-Au DENPs have an extended blood circulation time and can be cleared from the major organs within 24 h. The strategy to use facile dendrimer technology to design dual mode contrast agents may be extended to prepare multifunctional platforms for targeted multimode molecular imaging of various biological systems.

摘要

我们报告了镝负载的树状大分子包裹的金纳米粒子(Gd-Au DENPs)的合成、表征及其在双模式计算机断层扫描(CT)/磁共振(MR)成像中的应用。在这项研究中,我们使用胺末端的第五代聚酰胺-胺(G5.NH2)树枝状大分子,用镝螯合剂和聚乙二醇(PEG)单甲醚进行修饰,作为模板来合成金纳米粒子(AuNPs)。然后通过 Gd(III)的螯合和剩余树状大分子末端胺基的乙酰化反应,形成多功能 Gd-Au DENPs。通过不同的技术对形成的 Gd-Au DENPs 进行了表征。我们表明,形成的 Gd-Au DENPs 在 Au 浓度高达 50 μM 时具有胶体稳定性和非细胞毒性。由于 AuNPs 和 Gd(III)两种放射性高密度成像元素存在于一个 NP 系统中,形成的 Gd-Au DENPs 既具有磁共振成像模式的 r₁弛豫率,又具有 CT 成像模式的 X 射线衰减特性,这使得大鼠或小鼠的心、肝、肾和膀胱可以在 45 分钟的时间内进行 CT/MR 双模式成像。此外,体内分布研究表明,Gd-Au DENPs 具有延长的血液循环时间,可以在 24 小时内从主要器官中清除。使用简单的树枝状大分子技术设计双模式造影剂的策略可能会扩展到制备用于各种生物系统的靶向多模式分子成像的多功能平台。

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