Department of Chemistry, University of Connecticut, Storrs, CT 06269, USA.
J Mater Chem B. 2020 Jul 14;8(26):5627-5635. doi: 10.1039/d0tb00767f. Epub 2020 May 11.
This work highlights a multifunctional nanoscale material which can effectively compartmentalize small molecules and biomolecules into a single, micellar structure with programmable degradation properties resulting in highly controllable release properties. The nanomaterial consists of a ZIF-8 metal organic framework (MOF) encapsulated within a DNA surfactant micelle assembly, referred to as a nucleic acid nanocapsule (NAN). NANs have been demonstrated to enter cells through endocytosis and result in intracellular cargo release upon enzyme-triggered degradation. By combining the favorable properties of MOFs (large storage capacity) with those of NANs (triggerable release), we show diverse molecular cargo can be integrated into a single, highly programmable nanomaterial with controllable release profiles. The hybrid MOF-NANs exhibit double-gated regulation capabilities as evidenced by kinetic studies of encapsulated enzymes that indicate individual layers of the particle influence the overall enzymatic rate of turnover. The degradation of MOF-NANs can be controlled under multiple combined stimuli (i.e. varying pH, enzymes), enabling selective release profiles in solutions representative of more complex biological systems. Lastly, the enhanced control over the release of small molecules, proteins and plasmids, is evaluated through a combination of cell culture and in vitro fluorescence assays, indicating the potential of MOF-NANs for both therapeutic and diagnostic applications.
这项工作重点介绍了一种多功能纳米材料,它可以将小分子和生物分子有效地分隔到单个胶束结构中,具有可编程的降解特性,从而产生高度可控的释放特性。该纳米材料由 ZIF-8 金属有机骨架(MOF)封装在 DNA 表面活性剂胶束组装内组成,称为核酸纳米胶囊(NAN)。已经证明 NAN 可以通过内吞作用进入细胞,并在酶触发降解时导致细胞内货物释放。通过将 MOF 的有利特性(大存储容量)与 NAN 的有利特性(可触发释放)相结合,我们展示了可以将各种分子货物整合到具有可控释放特性的单个高度可编程纳米材料中。杂交 MOF-NAN 表现出双门控调节能力,这可以通过封装酶的动力学研究来证明,表明颗粒的单个层影响整体酶周转率。可以在多种组合刺激(例如 pH 值变化、酶)下控制 MOF-NAN 的降解,从而在更复杂的生物系统的代表溶液中实现选择性释放特性。最后,通过细胞培养和体外荧光测定的组合评估了对小分子、蛋白质和质粒释放的增强控制,表明 MOF-NAN 具有治疗和诊断应用的潜力。