26. Design and Combinatorial Synthesis of Biomimetic Multivariate Metal–Organic Frameworks for Efficient Drug Loading
Multivariate metal–organic frameworks (MOFs) covering diverse iso-reticular materials while encompassing tunable function through the spatial composition of the organic functional groups are an excellent starting point for developing sequence-dependent materials. There remains a demand for synthesizing an extensive library of multivariate MOFs for function-targeted selection, similar to the process of directed evolution in improving the function of proteins by selecting the best mutant from a large mutant library. The design of biomimetic multivariate MOFs (bMTV-MOFs) is reported that incorporate the panel of functionality presented in amino acids to enable the complexity and adjustability of proteins to the structure of MOFs. A total of 1089 MOFs, ranging from single-component to multivariate structures, are synthesized in a combinatorial manner for the delivery of the verteporfin, a photosensitive drug. Tertiary bMTV-MOFs demonstrated superiority in the adsorption and release of verteporfin. In vitro studies on various cancer cell lines demonstrated a 23 to 68-fold enhancement in efficacy for photodynamic therapy using the privileged A1F6H3 or A3D1H6 bMTV-MOFs over pristine MOFs.
多元金属有机骨架 (MOF) 涵盖多种等孔径材料，同时通过有机官能团的空间组成实现功能可调，是开发序列依赖性材料的绝佳起点。目前仍需合成一个庞大的多元 MOF 库，以便进行功能靶向筛选，类似于定向进化的过程，即通过从大型突变体库中筛选出最佳突变体来改善蛋白质的功能。据报道，仿生多元 MOF (bMTV-MOF) 的设计融合了氨基酸所呈现的一系列功能，从而实现了蛋白质的复杂性和对 MOF 结构的可调整性。共合成了 1089 种 MOF，涵盖单组分到多元结构，以组合方式用于递送光敏药物维替泊芬。三级 bMTV-MOF 在维替泊芬的吸附和释放方面表现出优异的性能。对各种癌细胞系进行的体外研究表明，与原始 MOF 相比，使用特权 A1F6H3 或 A3D1H6 bMTV-MOF 的光动力疗法疗效提高了 23 至 68 倍。