载锰介孔硅纳米粒子用于 MRI 细胞示踪研究中的信号增强。

Manganese-impregnated mesoporous silica nanoparticles for signal enhancement in MRI cell labelling studies.

机构信息

Département de chimie, Université Laval, Québec QC G1V 0A6, Canada.

出版信息

Nanoscale. 2013 Dec 7;5(23):11499-511. doi: 10.1039/c3nr02969g. Epub 2013 Oct 31.

Abstract

Mesoporous silica nanoparticles (MSNs) are used in drug delivery and cell tracking applications. As Mn(2+) is already implemented as a "positive" cell contrast agent in preclinical imaging procedures (in the form of MnCl2 for neurological studies), the introduction of Mn in the porous network of MSNs would allow labelling cells and tracking them using MRI. These particles are in general internalized in endosomes, an acidic environment with high saline concentration. In addition, the available MSN porosity could also serve as a carrier to deliver medical/therapeutic substances through the labelled cells. In the present study, manganese oxide was introduced in the porous network of MCM-48 silica nanoparticles (Mn-M48SNs). The particles exhibit a narrow size distribution (140 nm diam.) and high porosity (60% vol.), which was validated after insertion of Mn. The resulting Mn-M48SNs were characterized by TEM, N2 physisorption, and XRD. Evidence was found with H2-TPR, and XPS characterization, that Mn(II) is the main oxidation state of the paramagnetic species after suspension in water, most probably in the form of Mn-OOH. The colloidal stability as a function of time was confirmed by DLS in water, acetate buffer and cell culture medium. In NMR data, no significant evidence of Mn(2+) leaching was found in Mn-M48SNs in acidic water (pH 6), up to 96 hours after suspension. High longitudinal relaxivity values of r1 = 8.4 mM(-1) s(-1) were measured at 60 MHz and 37 °C, with the lowest relaxometric ratios (r2/r1 = 2) reported to date for a Mn-MSN system. Leukaemia cells (P388) were labelled with Mn-M48SNs and nanoparticle cell internalization was confirmed by TEM. Finally, MRI contrast enhancement provided by cell labelling with escalated incubation concentrations of Mn-M48SNs was quantified at 1 T. This study confirmed the possibility of efficiently confining Mn into M48SNs using incipient wetness, while maintaining an open porosity and relatively high pore volume. Because these Mn-labelled M48SNs express strong "positive" contrast media properties at low concentrations, they are potentially applicable for cell tracking and drug delivery methodologies.

摘要

介孔硅纳米粒子(MSNs)被应用于药物输送和细胞示踪应用。由于 Mn(2+) 已经作为一种“阳性”细胞对比剂在临床前成像程序中得到应用(以 MnCl2 的形式用于神经科学研究),因此将 Mn 引入 MSNs 的多孔网络中,可以使用 MRI 标记细胞并对其进行跟踪。这些颗粒通常被内吞到内涵体中,这是一种具有高盐浓度的酸性环境。此外,可用的 MSN 孔隙率也可以作为载体,通过标记的细胞输送医疗/治疗物质。在本研究中,在 MCM-48 硅纳米粒子(Mn-M48SNs)的多孔网络中引入了氧化锰。这些颗粒表现出窄的粒径分布(140nm 直径)和高的孔隙率(60%体积),在插入 Mn 后得到验证。通过 TEM、N2 物理吸附和 XRD 对得到的 Mn-M48SNs 进行了表征。通过 H2-TPR 和 XPS 表征,发现水悬浮后,Mn 的主要氧化态为 Mn(II),很可能是以 Mn-OOH 的形式存在。通过 DLS 在水、醋酸盐缓冲液和细胞培养基中的测试,证实了胶体稳定性随时间的变化。在 NMR 数据中,在酸性水(pH 6)中,Mn-M48SNs 在 96 小时内没有发现明显的 Mn(2+)浸出的证据。在 60MHz 和 37°C 下测量到的纵向弛豫率 r1 值为 8.4mM(-1)s(-1),这是迄今为止报道的 Mn-MSN 系统中最低的弛豫比(r2/r1=2)。用 Mn-M48SNs 标记白血病细胞(P388),并用 TEM 证实了纳米颗粒的细胞内化。最后,在 1T 下定量了 Mn-M48SNs 浓度递增孵育后细胞标记提供的 MRI 对比增强。这项研究证实了使用初始湿化学法有效地将 Mn 限制在 M48SNs 中的可能性,同时保持开放的多孔性和相对较高的孔体积。由于这些 Mn 标记的 M48SNs 在低浓度下表现出强烈的“阳性”对比剂性质,因此它们可能适用于细胞跟踪和药物输送方法。

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