Enhanced anticancer activity of N,N-bis(5-ethyl-2-hydroxybenzyl)methylamine (EMD) hydrophobic drug encapsulated in β-cyclodextrin nanosponges

IF 4.7 3区材料科学 Q2 CHEMISTRY, PHYSICAL Colloid and Interface Science Communications Pub Date : 2024-09-01 DOI:10.1016/j.colcom.2024.100803

Sunisa Thongsom , Paolo Di Gianvincenzo , Suchittra Konkankun , Agustín Blachman , Silvestre Bongiovanni Abel , Natcha Madared , Chanchai Boonla , Pithi Chanvorachote , Sergio E. Moya

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Abstract

N, N-bis (5-ethyl-2-hydroxybenzyl) methylamine (EMD) is a synthetic benzoxazine dimer compound. EMD targets and degrades the pro-oncogenic transcription factor c-Myc, initiating apoptosis in cancer cells. However, its use is restricted because of poor aqueous solubility and in physiological media. Cyclodextrin nanosponges (CN), a type of supramolecular macrocyclic polymer nanoparticles with hydrophobic cavities but soluble in water, are utilized here to load EMD in order to enhance its solubility. CNs with three different molar ratios of β-cyclodextrin (βCD)-to-citric acid crosslinker are synthesized: CN1 (βCD/citric acid 1:3), CN2 (βCD/citric acid 1:5), and CN3 (βCD/citric acid 1:8), and then loaded with EMD. EMD-CN2 exhibits a significantly higher solubilization efficiency (579.1 μg/mL) compared to the free EMD (59.09 μg/mL). The increased aqueous solubility of CN encapsulated EMD enhanced its anti-cancer efficacy. In vitro cytotoxicity, colony formation inhibition, and c-Myc suppression of EMD in cancer cells (A549 and HCT116) are improved over free EMD administration.

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增强包裹在β-环糊精纳米海绵中的 N,N-双（5-乙基-2-羟基苄基）甲胺（EMD）疏水性药物的抗癌活性

N，N-双（5-乙基-2-羟基苄基）甲胺（EMD）是一种合成的苯并恶嗪二聚化合物。EMD 可靶向降解促癌转录因子 c-Myc，启动癌细胞凋亡。然而，由于其水溶性和在生理介质中的溶解性较差，其使用受到了限制。环糊精纳米海绵（CN）是一种具有疏水性空腔但可溶于水的超分子大环聚合物纳米颗粒，本研究利用环糊精纳米海绵来负载 EMD，以提高其溶解性。我们合成了三种不同摩尔比的β-环糊精（βCD）-柠檬酸交联剂的 CN：CN1（βCD/柠檬酸 1:3）、CN2（βCD/柠檬酸 1:5）和 CN3（βCD/柠檬酸 1:8），然后装入 EMD。与游离 EMD（59.09 μg/mL）相比，EMD-CN2 的增溶效率（579.1 μg/mL）明显更高。CN 包裹的 EMD 的水溶性增加，从而提高了其抗癌功效。与游离EMD相比，EMD在癌细胞（A549和HCT116）中的体外细胞毒性、集落形成抑制和c-Myc抑制作用均有所改善。

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来源期刊

Colloid and Interface Science Communications Materials Science-Materials Chemistry

CiteScore

9.40

自引率

6.70%

发文量

125

审稿时长

43 days

期刊介绍： Colloid and Interface Science Communications provides a forum for the highest visibility and rapid publication of short initial reports on new fundamental concepts, research findings, and topical applications at the forefront of the increasingly interdisciplinary area of colloid and interface science.