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具有超高体内清除效率的黑色素-锰纳米颗粒,可用作肿瘤靶向 T 磁共振成像造影剂。

Melanin-manganese nanoparticles with ultrahigh efficient clearance in vivo for tumor-targeting T magnetic resonance imaging contrast agent.

机构信息

Department of imaging of Shanxi Provincial Cancer Hospital, Molecular Imaging Precision Medical Collaborative Innovation Center, Shanxi Medical University, Platform of Shanxi Scientific and Technological Innovation, Taiyuan 030001, China.

出版信息

Biomater Sci. 2017 Dec 19;6(1):207-215. doi: 10.1039/c7bm00635g.

Abstract

Endogenous biomaterials in organisms, with native biocompatibility and biodegradability, appear more advantageous in the development of nanoscale diagnostic and therapeutic systems for future clinical translation. Herein, a novel tumor-targeting Magnetic Resonance Imaging (MRI) contrast agent was developed based on Mn-chelating ultrasmall water-soluble melanin nanoparticles (MNP-PEG-Mn). The nanoparticles, with a size of about 5.6 nm, presented high chelation stability and showed negligible cytotoxicity as estimated by MTT assay. Moreover, the r longitudinal relaxivity (20.56 mM s) of MNP-PEG-Mn was much higher than that of Gadodiamide (6.00 mM s), which is a clinically approved MRI contrast agent. In vivo MRI experiments revealed excellent tumor-targeting specificity after tumor-bearing mice were intravenously injected with MNP-PEG-Mn. Additionally, MNP-PEG-Mn could be excreted via renal and hepatobiliary pathways with negligible toxicity to body tissues. These preliminary results indicated the clinically translatable potential of MNP-PEG-Mn as a T MRI contrast agent for tumor-targeted imaging.

摘要

内源性生物材料在生物体内具有天然的生物相容性和可降解性,在开发用于未来临床转化的纳米级诊断和治疗系统方面具有更大的优势。在此,基于 Mn 螯合的超小水溶性黑色素纳米颗粒(MNP-PEG-Mn)开发了一种新型的肿瘤靶向磁共振成像(MRI)造影剂。该纳米颗粒的尺寸约为 5.6nm,具有很高的螯合稳定性,通过 MTT 测定法估计其细胞毒性可忽略不计。此外,MNP-PEG-Mn 的 r1 纵向弛豫率(20.56mM s)远高于临床批准的 MRI 造影剂钆喷酸葡胺(6.00mM s)。在荷瘤小鼠静脉注射 MNP-PEG-Mn 后进行体内 MRI 实验,显示出优异的肿瘤靶向特异性。此外,MNP-PEG-Mn 可以通过肾脏和肝胆途径排泄,对身体组织几乎没有毒性。这些初步结果表明,MNP-PEG-Mn 作为 T1 MRI 造影剂用于肿瘤靶向成像具有临床转化的潜力。

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