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在多种小鼠模型中磁性纳米立方、纳米团簇和纳米棒的生物分布和肿瘤 MRI 对比增强。

Biodistribution and Tumors MRI Contrast Enhancement of Magnetic Nanocubes, Nanoclusters, and Nanorods in Multiple Mice Models.

机构信息

National University of Science and Technology (MISIS), Moscow 119049, Russia.

M.V. Lomonosov Moscow State University, Moscow 119991, Russia.

出版信息

Contrast Media Mol Imaging. 2018 Sep 24;2018:8264208. doi: 10.1155/2018/8264208. eCollection 2018.

Abstract

Magnetic resonance imaging (MRI) is a powerful technique for tumor diagnostics. Iron oxide nanoparticles (IONPs) are safe and biocompatible tools that can be used for further enhancing MR tumor contrasting. Although numerous IONPs have been proposed as MRI contrast agents, low delivery rates to tumor site limit its application. IONPs accumulation in malignancies depends on both IONPs characteristics and tumor properties. In the current paper, three differently shaped Pluronic F-127-modified IONPs (nanocubes, nanoclusters, and nanorods) were compared side by side in three murine tumor models (4T1 breast cancer, B16 melanoma, and CT26 colon cancer). Orthotopic B16 tumors demonstrated more efficient IONPs uptake than heterotopic implants. Magnetic nanocubes (MNCb) had the highest r2-relaxivity in vitro (300 mM·s) compared with magnetic nanoclusters (MNCl, 104 mM·s) and magnetic nanorods (MNRd, 51 mM·s). As measured by atomic emission spectroscopy, MNCb also demonstrated better delivery efficiency to tumors (3.79% ID) than MNCl (2.94% ID) and MNRd (1.21% ID). Nevertheless, MNCl overperformed its counterparts in tumor imaging, providing contrast enhancement in 96% of studied malignancies, whereas MNCb and MNRd were detected by MRI in 73% and 63% of tumors, respectively. Maximum MR contrasting efficiency for MNCb and MNCl was around 6-24 hours after systemic administration, whereas for MNRd maximum contrast enhancement was found within first 30 minutes upon treatment. Presumably, MNRd poor MRI performance was due to low r2-relaxivity and rapid clearance by lungs (17.3% ID) immediately after injection. MNCb and MNCl were mainly captured by the liver and spleen without significant accumulation in the lungs, kidneys, and heart. High biocompatibility and profound accumulation in tumor tissues make MNCb and MNCl the promising platforms for MRI-based tumor diagnostics and drug delivery.

摘要

磁共振成像(MRI)是肿瘤诊断的有力技术。氧化铁纳米粒子(IONPs)是安全且生物相容的工具,可用于进一步增强 MR 肿瘤对比。尽管已经提出了许多 IONPs 作为 MRI 对比剂,但向肿瘤部位的低递送率限制了其应用。IONPs 在恶性肿瘤中的积累取决于 IONPs 的特性和肿瘤的特性。在当前的论文中,三种不同形状的 Pluronic F-127 修饰的 IONPs(纳米立方体、纳米团簇和纳米棒)在三种鼠肿瘤模型(4T1 乳腺癌、B16 黑色素瘤和 CT26 结肠癌)中进行了并排比较。与异位植入物相比,原位 B16 肿瘤具有更高的 IONPs 摄取效率。与磁性纳米团簇(MNCl,104 mM·s)和磁性纳米棒(MNRd,51 mM·s)相比,磁性纳米立方体(MNCb)在体外具有最高的 r2 弛豫率(300 mM·s)。通过原子发射光谱法测量,MNCb 向肿瘤的递送效率也优于 MNCl(2.94% ID)和 MNRd(1.21% ID)。然而,MNCl 在肿瘤成像方面表现优于其同类产品,在研究的 96%的恶性肿瘤中提供了对比度增强,而 MNCb 和 MNRd 分别在 73%和 63%的肿瘤中通过 MRI 检测到。MNCb 和 MNCl 的最大 MR 对比增强效率在系统给药后约 6-24 小时,而 MNRd 的最大对比增强在治疗后 30 分钟内即可发现。推测 MNRd 的 MRI 性能不佳是由于其 r2 弛豫率低且在注射后立即通过肺部(17.3% ID)快速清除。MNCb 和 MNCl 主要被肝脏和脾脏捕获,而在肺部、肾脏和心脏中没有明显积累。高生物相容性和在肿瘤组织中的深度积累使 MNCb 和 MNCl 成为基于 MRI 的肿瘤诊断和药物输送的有前途的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a0d/6174815/7a0427b191fc/CMMI2018-8264208.001.jpg

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