Utilizing metal–organic frameworks (MOFs) as a biological carrier can lower the amount of the active pharmaceutical ingredient (API) required in cancer treatments to provide a more efficacious therapy. In this work, we have developed a temperature treatment process for delaying the release of a model drug compound from the pores of NU-1000 and NU-901, while taking care to utilize these MOFs’ large pore volume and size to achieve exceptional model drug loading percentages over 35 wt %. Video-rate super-resolution microscopy reveals movement of MOF particles when located outside of the cell boundary, and their subsequent immobilization when taken up by the cell. Through the use of optical sectioning structured illumination microscopy (SIM), we have captured high-resolution 3D images showing MOF uptake by HeLa cells over a 24 h period. We found that addition of a model drug compound into the MOF and the subsequent temperature treatment process does not affect the rate of MOF uptake by the cell. Endocytosis analysis revealed that MOFs are internalized by active transport and that inhibiting the caveolae-mediated pathway significantly reduced cellular uptake of MOFs. Encapsulation of an anticancer therapeutic, alpha-cyano-4-hydroxycinnamic acid (α-CHC), and subsequent temperature treatment produced loadings of up to 81 wt % and demonstrated efficacy at killing cells beyond the burst release effect.

中文翻译：

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高度多孔的含锆金属-有机骨架的温度处理延长了药物的释放

利用金属有机框架（MOF）作为生物载体可以降低癌症治疗中所需的活性药物成分（API）的量，以提供更有效的治疗方法。在这项工作中，我们开发了一种温度处理工艺，以延迟模型药物化合物从NU-1000和NU-901的孔中释放，同时注意利用这些MOF的大孔体积和大小来获得优异的模型药物超过35重量％的负载百分比。视频速率超分辨率显微镜显示MOF颗粒位于细胞边界外时的运动，以及随后被细胞吸收后的固定。通过使用光学切片结构照明显微镜（SIM），我们已捕获了高分辨率的3D图像，显示了HeLa细胞在24小时内摄取的MOF。我们发现向MOF中添加模型药物化合物以及随后的温度处理过程不会影响细胞吸收MOF的速率。内吞作用分析显示，MOF通过主动转运而被内在化，并且抑制了MOF。小窝介导的途径显着降低了MOF的细胞摄取。抗癌治疗剂α-氰基-4-羟基肉桂酸（α-CHC）的封装以及随后的温度处理产生高达81 wt％的负载量，并证明了杀死细胞的功效超过了爆发释放效应。