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基于磁性层状双氢氧化物/Cu-MOFs-壳聚糖交联 κ-卡拉胶的 pH 敏感型生物相容性纳米载体的简便制备及其用于阿霉素的控制释放。

Facile preparation of a pH-sensitive biocompatible nanocarrier based on magnetic layered double hydroxides/Cu MOFs-chitosan crosslinked к-carrageenan for controlled doxorubicin delivery to breast cancer cells.

机构信息

Department of Chemistry, Tabriz Branch, Islamic Azad University, Tabriz, Iran.

Department of Chemistry, Tabriz Branch, Islamic Azad University, Tabriz, Iran.

出版信息

Colloids Surf B Biointerfaces. 2024 Nov;243:114122. doi: 10.1016/j.colsurfb.2024.114122. Epub 2024 Jul 24.

Abstract

Recently, the biocompatibility of hydrogel nanoparticles has gained considerable research attention in the field of drug delivery. In this regard, we design a pH-controlled nanocarrier based on magnetic layered double hydroxides/copper metal-organic framework-chitosan crosslinked к-carrageenan hydrogel nanoparticles (LDH-FeO/Cu MOF-DOX-CS@CAR) for targeted release from DOX to breast cancer cells. FT-IR, EDX, XRD, FE-SEM, VSM, and Zeta potential investigated the chemical structure of hydrogel nanoparticles. The encapsulation efficiency and drug loading capacity of the DOX were obtained to be 96.1 % and 9.6 %, respectively. The cumulative release of DOX from LDH-FeO/Cu MOF-DOX-CS@CAR at pH 5.5 and 7.4 after 72 h was 60.3 % and 22.6 %, respectively. These in vitro release results confirmed the controlled release and pH-response behavior of hydrogel nanoparticles. Also, the mechanism of DOX release from LDH-FeO/Cu MOF-DOX-CS@CAR hydrogel nanoparticles showed that the Korsmeyer-Peppas model with Fickian diffusion is the best-fitting model for describing the release behavior of DOX from hydrogel nanoparticles. The cellular cytotoxicity and DAPI tests of the prepared LDH and LDH-FeO/Cu MOF toward L929 non-cancerous cells and MCF-7 breast cancer cells confirm its relative biocompatibility and safety. Whereas, LDH-FeO/Cu MOF-DOX-CS@CAR hydrogel nanoparticles toward MCF-7 breast cancer cells had higher cytotoxicity effects due to the targeted and controlled release of DOX to MCF-7 cells. The in vitro DPPH, hemolysis assay, colloidal stability, and enzymatic degradation proved the excellent antioxidant activity (71.81 %), blood compatibility (less than 5 %), better stability, and biodegradation behavior of hydrogel nanoparticles. On these findings, the present study suggests the potential of the prepared LDH-FeO/Cu MOF-DOX-CS@CAR hydrogel nanoparticles as a pH-controlled drug delivery system for cancer treatment and various biomedical uses.

摘要

最近,水凝胶纳米粒子的生物相容性在药物传递领域引起了相当大的研究关注。在这方面,我们设计了一种基于磁性层状双氢氧化物/铜金属有机骨架-壳聚糖交联 к-卡拉胶水凝胶纳米粒子(LDH-FeO/Cu MOF-DOX-CS@CAR)的 pH 控制纳米载体,用于从 DOX 向乳腺癌细胞的靶向释放。FT-IR、EDX、XRD、FE-SEM、VSM 和 Zeta 电位研究了水凝胶纳米粒子的化学结构。DOX 的包封效率和载药量分别为 96.1%和 9.6%。在 72 小时后,LDH-FeO/Cu MOF-DOX-CS@CAR 在 pH 5.5 和 7.4 下的 DOX 累积释放率分别为 60.3%和 22.6%。这些体外释放结果证实了水凝胶纳米粒子的控制释放和 pH 响应行为。此外,LDH-FeO/Cu MOF-DOX-CS@CAR 水凝胶纳米粒子中 DOX 的释放机制表明,Korsmeyer-Peppas 模型与 Fickian 扩散最适合描述 DOX 从水凝胶纳米粒子中的释放行为。制备的 LDH 和 LDH-FeO/Cu MOF 对 L929 非癌细胞和 MCF-7 乳腺癌细胞的细胞毒性和 DAPI 试验证实了其相对生物相容性和安全性。然而,由于 DOX 向 MCF-7 细胞的靶向和控制释放,LDH-FeO/Cu MOF-DOX-CS@CAR 水凝胶纳米粒子对 MCF-7 乳腺癌细胞具有更高的细胞毒性作用。体外 DPPH、溶血试验、胶体稳定性和酶降解试验证明了水凝胶纳米粒子具有优异的抗氧化活性(71.81%)、血液相容性(小于 5%)、更好的稳定性和生物降解性。根据这些发现,本研究表明,所制备的 LDH-FeO/Cu MOF-DOX-CS@CAR 水凝胶纳米粒子作为 pH 控制药物传递系统用于癌症治疗和各种生物医学用途具有潜力。

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