Abstract

In this study, we have designed an anticancer drug delivery framework by a one-pot technique using a zeolitic imidazolate framework (ZIF) as the carrier. The chitosan-coated Aminopterin (AMT) loaded with zeolitic imidazolate framework (ZIF-90) CS@AMT@ZIF-90 (CAZ-90) for breast cancer cells. The particle’s outer layer changed Chitosan (CS), a pH-sensitive biomaterial, to increase the composite CAZ-90’s reactivity to pH during drug release. CAZ-90 displayed target-selective and pH-responsive by releasing a significant ratio of AMT under an acidic milieu and a considerably reduced amount of AMT in a normal milieu. Additionally, CAZ-90 was found to have low toxicity to normal Human umbilical vein endothelial cells (HUVECs) cells while inhibiting breast cancer 4T1, MDA-MB-231, and MCF-7 cells in vitro. Further, cell death was investigated by two different staining methods (AO-EB and DAPI nuclear staining). RNase-PI staining by flow cytometry techniques investigated the cell cycle arrest in breast (4T1, MDA-MB-231, and MCF-7) cancer cells. CAZ-90 showed high AMT drug loading, cancer-targeted release, and excellent biocompatibility in the related tests, making it a promising option for an anticancer drug delivery system.

摘要

在这项研究中，我们使用沸石咪唑酯骨架（ZIF）作为载体，通过一锅法技术设计了一种抗癌药物递送骨架。壳聚糖包被的氨基蝶呤 (AMT) 负载沸石咪唑酯骨架 (ZIF-90) CS@AMT@ZIF-90 (CAZ-90)，用于乳腺癌细胞。该颗粒的外层改变了壳聚糖 (CS)（一种 pH 敏感生物材料），以提高复合材料 CAZ-90 在药物释放过程中对 pH 的反应性。CAZ-90 通过在酸性环境下释放显着比例的 AMT 和在正常环境下释放显着减少的 AMT 量，表现出靶点选择性和 pH 响应性。此外，CAZ-90 对正常人脐静脉内皮细胞 (HUVEC) 细胞具有低毒性，同时在体外抑制乳腺癌 4T1、MDA-MB-231 和 MCF-7细胞。此外，通过两种不同的染色方法（AO-EB 和 DAPI 核染色）研究细胞死亡。通过流式细胞术技术进行 RNase-PI 染色研究了乳腺癌（4T1、MDA-MB-231 和 MCF-7）癌细胞的细胞周期停滞。CAZ-90在相关测试中表现出高AMT载药量、癌症靶向释放和优异的生物相容性，使其成为抗癌药物递送系统的有希望的选择。