通过点击化学合成后修饰 Curcumin@N3-bio-MOF-100 靶向药物递送系统的乳腺癌,Inorganic Chemistry

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通过点击化学合成后修饰 Curcumin@N3-bio-MOF-100 靶向药物递送系统的乳腺癌
Inorganic Chemistry ( IF 4.3 ) Pub Date : 2021-06-08 , DOI: 10.1021/acs.inorgchem.1c00538
Renata C Alves ₁ , Zachary M Schulte ₂ , Marcela T Luiz ₃ , Patrícia Bento da Silva ₄ , Regina C G Frem ₅ , Nathaniel L Rosi ₂ , Marlus Chorilli ₁

Affiliation

金属有机框架 (MOF) 为生物学和医学领域的应用提供了许多机会。它们广泛的化学成分使毒理学可接受的制剂成为可能，并且它们的高水平功能性使它们成为可能的应用作为治疗剂的递送系统。表面修饰已用于药物递送系统，以最大限度地减少它们与本体的相互作用，提高它们作为靶向载体的特异性。在此，我们讨论了一种使用“点击”化学将功能性叶酸 (FA) 分子锚定在 N ₃ -bio-MOF-100表面上以实现靶向肿瘤的载药 MOF 的策略。使用姜黄素 (CCM) 作为抗癌药物，我们观察到浸泡 N ₃后的载药封装效率 (DLE) 分别为 24.02 和 25.64%-bio-MOF-100 在 CCM 溶液中分别使用 1 天和 3 天。¹ H NMR 光谱、傅里叶变换红外光谱 (FTIR) 和液相色谱-质谱 (LC-MS)证实了 FA 合成后修饰的成功。刺激响应性药物释放研究表明，在酸性微环境下释放的 CCM 增加。此外，在 CCM@N ₃ -bio-MOF-100 和 CCM@N ₃ -bio-MOF-100/FA 载体存在的情况下，对 4T1（乳腺癌）细胞系进行了细胞活力测定，以确认其生物相容性. 此外，还进行了细胞摄取研究以评估肿瘤细胞的靶向性。

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Breast Cancer Targeting of a Drug Delivery System through Postsynthetic Modification of Curcumin@N3-bio-MOF-100 via Click Chemistry

Metal–organic frameworks (MOFs) offer many opportunities for applications across biology and medicine. Their wide range of chemical composition makes toxicologically acceptable formulation possible, and their high level of functionality enables possible applications as delivery systems for therapeutics agents. Surface modifications have been used in drug delivery systems to minimize their interaction with the bulk, improving their specificity as targeted carriers. Herein, we discuss a strategy to achieve a tumor-targeting drug-loaded MOF using “click” chemistry to anchor functional folic acid (FA) molecules on the surface of N₃-bio-MOF-100. Using curcumin (CCM) as an anticancer drug, we observed drug loading encapsulation efficiencies (DLEs) of 24.02 and 25.64% after soaking N₃-bio-MOF-100 in CCM solutions for 1 day and 3 days, respectively. The success of postsynthetic modification of FA was confirmed by ¹H NMR spectroscopy, Fourier transform infrared spectroscopy (FTIR), and liquid chromatography–mass spectrometry (LC-MS). The stimuli-responsive drug release studies demonstrated an increase of CCM released under acidic microenvironments. Moreover, the cell viability assay was performed on the 4T1 (breast cancer) cell line in the presence of CCM@N₃-bio-MOF-100 and CCM@N₃-bio-MOF-100/FA carriers to confirm its biological compatibility. In addition, a cellular uptake study was conducted to evaluate the targeting of tumor cells.

更新日期：2021-08-16

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