Department of Chemistry, Rice University, Houston, TX 77005.
Sao Carlos Institute of Physics, University of Sao Paulo, Sao Carlos, Sao Paulo 13566-590, Brazil.
Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):6960-6965. doi: 10.1073/pnas.1701944114. Epub 2017 Jun 19.
Multifunctional nanoparticles for biomedical applications have shown extraordinary potential as contrast agents in various bioimaging modalities, near-IR photothermal therapy, and for light-triggered therapeutic release processes. Over the past several years, numerous studies have been performed to synthesize and enhance MRI contrast with nanoparticles. However, understanding the MRI enhancement mechanism in a multishell nanoparticle geometry, and controlling its properties, remains a challenge. To systematically examine MRI enhancement in a nanoparticle geometry, we have synthesized MRI-active Au nanomatryoshkas. These are Au core-silica layer-Au shell nanoparticles, where Gd(III) ions are encapsulated within the silica layer between the inner core and outer Au layer of the nanoparticle (Gd-NM). This multifunctional nanoparticle retains its strong near-IR Fano-resonant optical absorption properties essential for photothermal or other near-IR light-triggered therapy, while simultaneously providing increased T contrast in MR imaging by concentrating Gd(III) within the nanoparticle. Measurements of Gd-NM revealed a strongly enhanced T relaxivity (r ∼ 24 mM⋅s) even at 4.7 T, substantially surpassing conventional Gd(III) chelating agents (r ∼ 3 mM⋅s at 4.7 T) currently in clinical use. By varying the thickness of the outer gold layer of the nanoparticle, we show that the observed relaxivities are consistent with Solomon-Bloembergen-Morgan (SBM) theory, which takes into account the longer-range interactions between the encapsulated Gd(III) and the protons of the HO molecules outside the nanoparticle. This nanoparticle complex and its MRI T-enhancing properties open the door for future studies on quantitative tracking of therapeutic nanoparticles in vivo, an essential step for optimizing light-induced, nanoparticle-based therapies.
用于生物医学应用的多功能纳米粒子作为各种生物成像模式中的对比剂、近红外光热疗法以及光触发治疗释放过程中的应用显示出了非凡的潜力。在过去的几年中，已经进行了许多研究来合成和增强具有磁共振成像（MRI）对比功能的纳米粒子。然而，理解多壳纳米粒子结构中的 MRI 增强机制并控制其性质仍然是一个挑战。为了系统地研究纳米粒子结构中的 MRI 增强，我们合成了具有 MRI 活性的 Au 纳米多面体。这些是 Au 核-二氧化硅层-Au 壳纳米粒子，其中 Gd（III）离子被包裹在纳米粒子内层核和外层 Au 层之间的二氧化硅层内（Gd-NM）。这种多功能纳米粒子保留了其强烈的近红外 Fano 共振光吸收特性，对于光热或其他近红外光触发治疗至关重要，同时通过将 Gd（III）集中在纳米粒子内来提高磁共振成像中的 T 对比。对 Gd-NM 的测量显示，即使在 4.7 T 下，T 弛豫率（r ∼ 24 mM⋅s）也得到了显著增强，大大超过了目前临床使用的常规 Gd（III）螯合剂（r ∼ 3 mM⋅s 在 4.7 T 下）。通过改变纳米粒子外层 Au 层的厚度，我们表明观察到的弛豫率与 Solomon-Bloembergen-Morgan（SBM）理论一致，该理论考虑了包裹的 Gd（III）与纳米粒子外的 HO 分子质子之间的长程相互作用。这种纳米粒子复合物及其 MRI T 增强特性为未来在体内对治疗性纳米粒子进行定量跟踪的研究开辟了道路，这是优化基于光诱导的纳米粒子治疗的关键步骤。
