School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
ACS Appl Mater Interfaces. 2022 Aug 17;14(32):36366-36378. doi: 10.1021/acsami.2c07450. Epub 2022 Jul 27.
The introduction of different pore diameters in metal organic frameworks (MOFs) could adjust their drug delivery performance. MOFs with customized structures have potential application value in targeted drug delivery. However, no research on this topic has been found so far. In this report, isoreticular metal organic frameworks (IRMOFs) have been taken as a typical case of tailor-made MOFs, the pore size of which is enlarged (average BJH pore sizes of about 2.43, 3.06, 5.47, and 6.50 nm were determined for IRMOF-1, IRMOF-8, IRMOF-10, and IRMOF-16, respectively), emphasizing the relationship between pore size and model drugs (Oridonin, ORI) and clarifying its potential working mechanism. IRMOF-1, whose pore size matches the size of ORI, has an outstanding drug loading capacity (57.93% by wt) and release profile (about 90% in 24 h at pH 7.4). IRMOF-1 was further coated with polyethylene glycol (PEG) modified with a cell penetrating peptide (CPP44) bound to M160 (CD163L1) protein for targeting of hepatic tumor lines. This nanoplatform (CPP44-PEG@ORI@IRMOF-1) exhibited acid-responsive drug release behavior (37.86% in 10 h at pH 7.4 and 66.66% in 10 h at pH 5.5) and significantly enhanced antitumor effects. The results of cell targeting and in vivo animal imaging indicated that CPP44-PEG@ORI@IRMOF-1 may serve as a tumor-selective drug delivery nanoplatform. Toxicity assessment confirmed that PEGylated IRMOF-1 did not cause organ or systemic toxicity. Furthermore, it is encouraging that the IRMOF-based targeted drug delivery system with pore size modulation showed rapid clearance (most administered NPs are metabolized from urine and feces within 1 week) and avoided accumulation in the body, indicating their promise for biomedical applications. This MOF-based aperture modulation combined with a targeted modification strategy might find broad applications in cancer theranostics. Thus, it is convenient to customize personalized MOFs according to the size of drug molecules in future research.
不同孔径的金属有机骨架（MOFs）的引入可以调节其药物输送性能。具有定制结构的 MOFs 在靶向药物输送中有潜在的应用价值。然而，到目前为止，还没有关于这一主题的研究。在本报告中，等孔金属有机骨架（IRMOFs）被用作定制 MOFs 的典型案例，其孔径增大（IRMOF-1、IRMOF-8、IRMOF-10 和 IRMOF-16 的平均 BJH 孔径分别约为 2.43、3.06、5.47 和 6.50nm），强调了孔径与模型药物（冬凌草甲素，ORI）的关系，并阐明了其潜在的工作机制。IRMOF-1 的孔径与 ORI 的大小相匹配，具有出色的载药能力（按重量计为 57.93%）和释放特性（在 pH7.4 下约 24 小时内释放 90%）。IRMOF-1 进一步用与 M160（CD163L1）蛋白结合的细胞穿透肽（CPP44）修饰的聚乙二醇（PEG）包覆，用于靶向肝肿瘤系。该纳米平台（CPP44-PEG@ORI@IRMOF-1）表现出酸响应性药物释放行为（在 pH7.4 下 10 小时内释放 37.86%，在 pH5.5 下 10 小时内释放 66.66%），并显著增强了抗肿瘤效果。细胞靶向和体内动物成像的结果表明，CPP44-PEG@ORI@IRMOF-1 可能作为一种肿瘤选择性药物递送纳米平台。毒性评估证实 PEG 化的 IRMOF-1 不会引起器官或全身毒性。此外，令人鼓舞的是，具有孔径调节的基于 MOF 的靶向药物输送系统表现出快速清除（大多数给予的 NPs 在 1 周内从尿液和粪便中代谢），并避免在体内积累，表明它们在生物医学应用中具有广阔的前景。这种基于 MOF 的孔径调节与靶向修饰策略相结合，可能在癌症治疗学中得到广泛应用。因此，在未来的研究中，根据药物分子的大小定制个性化 MOF 将变得更加方便。
