文献：Highly Stable and Long-Circulating Metal-Organic Frameworks Nanoprobes for Sensitive Tumor Detection In Vivo

文献链接：https://advanced.onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201900761

作者：Ruili Zhang, Chaoqiang Qiao, Qian Jia, Yongdong Wang, Huimin Huang, Wanwan Chang, He Wang, Hao Zhang, and Zhongliang Wang

相关产品：

HOOC-PEG-NH2 5000（羧基-聚乙二醇-氨基5000）

mPEG-COOH 5000（甲氧基聚乙二醇-羧基5000）

原文摘要：

High stability and extended circulation time in vivo are quite favorable for practical biomedical applications of nanomaterials, because they greatly facilitate the preferential tumor accumulation of nanomaterials, resulting in enhanced signal fidelity for imaging and improved therapeutic effect for treatment. Although many surface modification approaches have been employed to improve the stability and circulating behavior of nanomaterials, it still remains challenging in acquiring stable and long-lasting nanomaterials for in vivo bioimaging and therapy, especially for nanoscale metal-organic frameworks (NMOFs) due to their intrinsic instability in physiological conditions. Herein, a facile, one-step strategy is reported to encapsulate the zirconium (Zr)-based NMOF UiO-66 within 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) lipid bilayer (DOPA-LB). Contrary to UiO-66 NMOFs functionalized with polyethylene glycol, the obtained UiO-66@DOPA-LB presents significantly enhanced stability and impressive blood circulation time, allowing a higher accumulation of UiO-66@DOPA-LB in the tumor tissue. Benefited from these meritorious features, UiO-66@DOPA-LB labeled with near-infrared dye, IRDye 800CW, can not only achieve highly sensitive imaging of breast cancer tumor (5 mm), but also exhibits superior capability for early tumor (1–2 mm) detection. This study enriches the surface modification approach of NMOFs, and is of great importance for practical application of NMOFs in biomedical areas.

HOOC-PEG-NH2 5000：聚乙二醇是一种具有良好水溶性的聚合物，它的主链由乙二醇单元（-CH2CH2O -）重复构成。在 “HOOC - PEG - NH2” 这种结构中，羧基和氨基分别位于聚乙二醇链的两端。羧基可以参与酯化、酰胺化等反应，例如它可以和含有羟基的化合物发生酯化反应，生成酯键；氨基可以和含有羧基或其他活性基团（如酰氯、酸酐等）的化合物发生反应，形成酰胺键。

mPEG - COOH 5000 表示甲氧基聚乙二醇羧基化合物，分子量为 5000。其中 “m” 代表甲氧基（CH3O -），它位于聚乙二醇（PEG）链的一端，而羧基（-COOH）位于聚乙二醇链的另一端。聚乙二醇部分是由多个乙二醇单元（-CH2CH2O -）重复连接而成的。这种结构使得它既有聚乙二醇良好的水溶性、生物相容性等特点，又有羧基的化学活性。基于HOOC-PEG-NH2 5000，mPEG - COOH 5000 的性能，该文献介绍如下：

图：制备及作用示意

PEG（UiO- 66-PEG）对UiO-66纳米颗粒的表面功能化：

将HOOC-PEG和UiO-66分散在纯水中，并在室温下搅拌过夜。获得的UiO-66-PEG用纯水洗涤，通过离心收集，并在纯水、培养基或PBS中重悬。

UiO-66和UiO-66@DOPA-LB的荧光标记：

用NIR荧光染料IR-800标记UiO-66纳米颗粒，IR-800-NHS和HOOC-PEG-NH2在200µL PBS中混合，然后在室温下搅拌。然后将混合物加入到UiO-66-PEG水溶液中，并在室温下摇晃过夜。将得到的UiO-66-PEG-IR-800用纯水洗涤，通过离心收集，并在纯水、培养基或PBS中重悬。

图：电镜图像

结论：

该文献成功合成了UiO-66和 UiO-66@DOPA-LB，产物相比于其他产品展现出良好的性能。HOOC-PEG在改性时能使物质表面功能化，调节尺寸和稳定性，改善生物相容性和化合物负载能力等。HOOC-PEG-NH2在荧光标记时作为“桥梁”能够改善标记物性能图增加水溶性、降低非特异性吸附等，调节空间，提高标记稳定性。本文献丰富了表面改性方法，对NMOFs在生物医学领域的实际应用具有重要意义。