Nanoscale metal-organic frameworks for biomedical imaging and drug delivery.
Nanoscale metal-organic frameworks for biomedical imaging and drug delivery.
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DOI：
10.1021/ar200028a
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发表时间：
2011-10-18
影响因子：
18.3
通讯作者：
Lin, Wenbin
中科院分区：
文献类型：
--
作者：
Della Rocca, Joseph;Liu, Demin;Lin, Wenbin
金属-有机骨架（MOFs）是一类由多齿桥连配体和金属连接点自组装而成的杂化材料，已被研究用于各种应用。最近，这些材料已经缩小到纳米尺寸，本帐户详细介绍了用于生物医学应用的纳米级金属有机框架（NMOFs）的发展。与传统的纳米药物相比，NMOFs具有几个潜在的优势，例如它们的结构和化学多样性，它们的高负载能力和它们固有的生物降解性。在相对温和的条件下，NMOFs可以作为结晶或无定形材料获得。颗粒组成、尺寸和形态可以容易地调整以优化最终颗粒性质。研究人员采用了两种一般策略来使用NMOFs递送活性剂：通过将活性剂并入框架中或通过将活性剂装载到NMOFs的孔和通道中。用二氧化硅涂层或有机聚合物对NMOF表面进行改性可提高NMOF稳定性，微调其性能，并赋予额外的功能。NMOFs的初步生物医学应用集中在它们作为成像造影剂和分子治疗剂的递送载体的用途。由于NMOF可以携带大量顺磁性金属离子，因此它们已被广泛探索作为磁共振成像（MRI）造影剂。含Gd 3+和Mn 2+的NMOF作为T1加权造影剂均显示出优异的功效，具有大的基于每金属和每颗粒的MR弛豫率。含Fe 3+的NMOF表现出良好的T2加权对比增强。在Wistar大鼠中静脉注射羧酸铁NMOF后，研究人员观察到肝脏和脾脏中的负信号增强，随着时间的推移而消失，表明NMOF的降解和清除。通过掺入发光或高Z元素结构单元，NMOF还用作光学成像或X射线计算机断层扫描（CT）成像的可行造影剂。将膜不可渗透的染料并入NMOFs中允许它们被癌细胞摄取，并且随着框架分解允许它们受控释放。NM 0 F已用于递送抗癌药物和其他化学治疗剂。通过使用前药作为结构单元或通过在合成后将前药连接到框架上，将顺铂前药以非常高的水平掺入NMOF中。这些NMOF被封装在二氧化硅壳内并靶向癌细胞。体外试验表明，靶向NMOFs具有类似的疗效顺铂，而非靶向NMOFs的活性较低。几种不同的治疗分子以前所未有的水平装载在多孔铁-羧酸盐NMOFs内。NMOF显示出持续的药物释放，没有突释效应，体外试验表明，纳米胶囊化的药物具有类似的疗效，游离药物。虽然仍处于非常早期的发展阶段，但NMOFs已经显示出作为纳米医学新平台的巨大潜力。用于生产NMOF的组成可调谐性和温和的合成条件应允许掺入其他成像剂和治疗剂并将其有效递送至体内靶向细胞。
Metal–organic frameworks (MOFs), a class of hybrid materials formed by the self-assembly of polydentate bridging ligands and metal-connecting points, have been studied for a variety of applications. Recently, these materials have been scaled down to nanometer sizes, and this Account details the development of nanoscale metal–organic frameworks (NMOFs) for biomedical applications. NMOFs possess several potential advantages over conventional nanomedicines such as their structural and chemical diversity, their high loading capacity, and their intrinsic biodegradability. Under relatively mild conditions, NMOFs can be obtained as either crystalline or amorphous materials. The particle composition, size, and morphology can be easily tuned to optimize the final particle properties. Researchers have employed two general strategies to deliver active agents using NMOFs: by incorporating active agents into the frameworks or by loading active agents into the pores and channels of the NMOFs. The modification of NMOF surfaces with either silica coatings or organic polymers improves NMOF stability, fine-tunes their properties, and imparts additional functionality. Preliminary biomedical applications of NMOFs have focused on their use as delivery vehicles for imaging contrast agents and molecular therapeutics. Because NMOFs can carry large amounts of paramagnetic metal ions, they have been extensively explored as magnetic resonance imaging (MRI) contrast agents. Both Gd3+- and Mn2+-containing NMOFs have shown excellent efficacy as T1-weighted contrast agents with large per metal- and per particle-based MR relaxivities. Fe3+-containing NMOFs have demonstrated excellent T2-weighted contrast enhancement. Upon intravenous injection of iron carboxylate NMOFs in Wistar rats, researchers observed negative signal enhancement in the liver and spleen, which dissipated over time, indicating the degradation and clearance of the NMOF. Through the incorporation of luminescent or high Z element building blocks, NMOFs have also served as viable contrast agents for optical imaging or X-ray computed tomography (CT) imaging. Incorporation of membrane impermeable dyes into NMOFs allowed for their uptake by cancer cells and for their controlled release as the framework decomposed. NMOFs have been used to deliver anticancer drugs and other chemotherapeutics. Cisplatin prodrugs were incorporated within NMOFs at exceptionally high levels, either through use of the prodrug as the building block or through attachment of the prodrug onto the framework after synthesis. These NMOFs were encapsulated within a silica shell and targeted to cancer cells. In vitro assays revealed that the targeted NMOFs possessed similar efficacy to cisplatin, while the nontargeted NMOFs were less active. Several different therapeutic molecules were loaded within porous iron-carboxylate NMOFs at unprecedented levels. The NMOF showed sustained drug release with no burst effect, and in vitro assays revealed that the nanoencapsulated drug possessed similar efficacy to the free drug. Although still at a very early stage of development, NMOFs have already shown great promise as a novel platform for nanomedicine. The compositional tunability and mild synthetic conditions used to produce NMOFs should allow for the incorporation of other imaging and therapeutic agents and their effective delivery to targeted cells in vivo.
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影响因子：
4.9
作者：
Aime, Carole;Nishiyabu, Ryuhei;Kimizuka, Nobuo
通讯作者：
Kimizuka, Nobuo
影响因子：
4.3
作者：
Aime, Carole;Nishiyahu, Ryuhei;Kimizuka, Nobuo
通讯作者：
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影响因子：
5
作者：
Broome, Dale R.;Girguis, Mark S.;Kirk, Gerald A.
通讯作者：
Kirk, Gerald A.
影响因子：
16.6
作者：
deKrafft, Kathryn E.;Xie, Zhigang;Lin, Wenbin
通讯作者：
Lin, Wenbin
影响因子：
41.2
作者：
Horcajada, Patricia;Chalati, Tamim;Gref, Ruxandra
通讯作者：
Gref, Ruxandra