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钆-天冬酰胺-阴离子线性球形树枝状大分子第二代 G2 复合物：新型纳米生物诊疗一体。

Gd-Asparagine-Anionic Linear Globular Dendrimer Second-Generation G2 Complexes: Novel Nanobiohybrid Theranostics.

机构信息

Department of Radiopharmacy and Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.

Drug Applied Research Center and Students' Research Committee, Tabriz University of Medical Science, Tabriz, Iran.

出版信息

Contrast Media Mol Imaging. 2017 Sep 26;2017:3625729. doi: 10.1155/2017/3625729. eCollection 2017.

DOI:10.1155/2017/3625729
PMID:29097918
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5635473/
Abstract

Designing a unique theranostic biocompatible, biodegradable, and cost-effective agent which is easy to be synthesized as a biohybrid material was the aim of this study. In this matter, asparagine attached to anionic linear globular dendrimer G2 (as a biocompatible, biodegradable, and cost-effective agent which is negatively charged nanosized and water soluble polymer that outweighs other traditionally used dendrimers) and finally contrast agent (Gd) was loaded (which made complexes) in synthesized asparagine-dendrimer. Observations revealed that, in addition to successful colon cancer and brain targeting, Gd-dendrimer-asparagine, the proposed theranostic agent, could increase T1 MR relaxation times, decrease T2 MR relaxation times significantly, and improve contrast of image as well as illustrating good cellular uptake based on florescent microscopy/flow cytometry and ICP-mass data. In addition to that, it increased tumor growth inhibition percentage (TGI%) significantly compared to FDA approved contrast agent, Magnevist. Totally, Gd3+-anionic linear globular dendrimer G2-asparagine could be introduced to the cancer imaging/therapy (theranostics) protocols after in vivo MR and fluorescent analysis and passing clinical trials. Hence, this nanotheranostic agent would be a promising candidate for brain drug delivery and imaging in the future.

摘要

本研究旨在设计一种独特的治疗诊断两用的生物相容性、可生物降解且具有成本效益的试剂，该试剂易于合成，可作为生物杂化材料。在这方面，天冬酰胺与阴离子线性球形树枝状大分子 G2（作为一种生物相容性、可生物降解且具有成本效益的试剂，是带负电荷的纳米级水溶性聚合物，优于其他传统使用的树枝状大分子）结合，最后将造影剂（Gd）负载（形成复合物）到合成的天冬酰胺-树枝状大分子中。观察结果表明，除了成功靶向结肠癌和脑肿瘤外，所提出的治疗诊断试剂 Gd-树枝状大分子-天冬酰胺还可以增加 T1MR 弛豫时间，显著降低 T2MR 弛豫时间，并改善图像对比度，荧光显微镜/流式细胞术和 ICP-质量数据表明其具有良好的细胞摄取能力。此外，与 FDA 批准的造影剂马根维显相比，它还显著提高了肿瘤生长抑制百分比（TGI%）。总的来说，Gd3+-阴离子线性球形树枝状大分子 G2-天冬酰胺在体内磁共振和荧光分析以及通过临床试验后，可以被引入癌症成像/治疗（治疗诊断）方案中。因此，这种纳米治疗诊断试剂将成为未来脑内药物输送和成像的有前途的候选物。

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