Abánades Lázaro Isabel, Haddad Salame, Sacca Sabrina, Orellana-Tavra Claudia, Fairen-Jimenez David, Forgan Ross S
WestCHEM School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow G12 8QQ, UK.
Adsorption & Advanced Materials Laboratory, Department of Chemical Engineering & Biotechnology, University of Cambridge, Pembroke Street, Cambridge CB2 3RA, UK.
Chem. 2017 Apr 13;2(4):561-578. doi: 10.1016/j.chempr.2017.02.005.
The high storage capacities and excellent biocompatibilities of metal-organic frameworks (MOFs) have made them emerging candidates as drug-delivery vectors. Incorporation of surface functionality is a route to enhanced properties, and here we report on a surface-modification procedure-click modulation-that controls their size and surface chemistry. The zirconium terephthalate MOF UiO-66 is (1) synthesized as ∼200 nm nanoparticles coated with functionalized modulators, (2) loaded with cargo, and (3) covalently surface modified with poly(ethylene glycol) (PEG) chains through mild bioconjugate reactions. At pH 7.4, the PEG chains endow the MOF with enhanced stability toward phosphates and overcome the "burst release" phenomenon by blocking interaction with the exterior of the nanoparticles, whereas at pH 5.5, stimuli-responsive drug release is achieved. The mode of cellular internalization is also tuned by nanoparticle surface chemistry, such that PEGylated UiO-66 potentially escapes lysosomal degradation through enhanced caveolae-mediated uptake. This makes it a highly promising vector, as demonstrated for dichloroacetic-acid-loaded materials, which exhibit enhanced cytotoxicity. The versatility of the click modulation protocol will allow a wide range of MOFs to be easily surface functionalized for a number of applications.
金属有机框架材料（MOFs）的高存储容量和出色的生物相容性使其成为新兴的药物递送载体候选材料。引入表面功能是增强其性能的一条途径，在此我们报道一种表面改性方法——点击调制，该方法可控制其尺寸和表面化学性质。对苯二甲酸锆MOF UiO - 66的制备过程如下：（1）合成尺寸约为200 nm、表面包覆有功能化调节剂的纳米颗粒；（2）装载药物；（3）通过温和的生物共轭反应，用聚乙二醇（PEG）链对其表面进行共价修饰。在pH 7.4时，PEG链使MOF对磷酸盐具有更高的稳定性，并通过阻断与纳米颗粒外部的相互作用克服了“突发释放”现象；而在pH 5.5时，则实现了刺激响应性药物释放。纳米颗粒的表面化学性质还可调节细胞内化模式，使得聚乙二醇化的UiO - 66可能通过增强小窝介导的摄取而避免溶酶体降解。这使其成为一种非常有前景的载体，以负载二氯乙酸的材料为例，其表现出增强的细胞毒性。点击调制方案的多功能性将使多种MOF能够轻松地进行表面功能化，以用于多种应用。
