通过锌盐变化和配体比例调整ZIF-8纳米颗粒的结构和功能以增强药物传递

IF 2.6 4区 材料科学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Derya Mete, Gülşah Şanlı-Mohamed
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引用次数: 0

摘要

多柔比星(DOX)是一种广泛使用的化疗药物,其临床应用受到全身毒性、快速清除和多药耐药的限制。金属-有机框架(MOFs),特别是沸石咪唑酸框架(ZIFs),由于其高载药能力、ph响应释放谱和良好的生物相容性,已成为克服这些限制的有前途的纳米载体。其中,ZIF-8因其在酸性肿瘤微环境中选择性释放药物的能力尤其具有吸引力。然而,ZIF-8的物理化学和生物学性质对合成参数,特别是锌盐前驱体的选择和Zn2+:配体的摩尔比非常敏感。在这项研究中,我们系统地研究了四种锌盐(硝酸锌、醋酸锌、氯化锌和溴化锌)和三种Zn2+:2-甲基咪唑的摩尔比(1:35、1:70和1:200)对负载dox的ZIF-8 (DOX@ZIF-8)纳米颗粒的合成、载药效率、释放行为和抗癌活性的影响。利用扫描电子显微镜(SEM)、动态光散射(DLS)、能量色散x射线能谱(EDX)、电感耦合等离子体发射光谱(ICP-OES)、热重分析(TGA)和布鲁诺尔-埃米特-泰勒(BET)表面积分析对纳米载体进行了表征。在生理(pH 7.4)和酸性(pH 5.0)条件下评估DOX的pH响应性释放。通过MTT法评估A549肺癌细胞的细胞毒性。此外,还进行了体外延时活细胞成像和伤口愈合试验,以评估细胞内药物摄取和细胞反应。我们的研究结果突出了锌盐选择和配体比例对ZIF-8结构-性能-功能关系的关键影响,为合理设计mof基纳米载体用于靶向癌症治疗提供了有价值的见解。图形抽象
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Structural and functional tuning of ZIF-8 nanoparticles via zinc salt variation and ligand ratio for enhanced drug delivery

Structural and functional tuning of ZIF-8 nanoparticles via zinc salt variation and ligand ratio for enhanced drug delivery

The clinical application of doxorubicin (DOX), a widely used chemotherapeutic agent, is limited by systemic toxicity, rapid clearance, and the development of multidrug resistance. Metal–organic frameworks (MOFs), particularly zeolitic imidazolate frameworks (ZIFs), have emerged as promising nanocarriers to overcome these limitations due to their high drug-loading capacity, pH-responsive release profiles, and favorable biocompatibility. Among them, ZIF-8 is especially attractive for its ability to selectively release drugs in acidic tumor microenvironments. However, the physicochemical and biological properties of ZIF-8 are highly sensitive to synthesis parameters, particularly the choice of zinc salt precursor and the Zn2+:ligand molar ratio. In this study, we systematically investigated the effects of four zinc salts (zinc nitrate, zinc acetate, zinc chloride, and zinc bromide) and three Zn2+:2-methylimidazole molar ratios (1:35, 1:70, and 1:200) on the synthesis, drug-loading efficiency, release behavior, and anticancer activity of DOX-loaded ZIF-8 (DOX@ZIF-8) nanoparticles. The resulting nanocarriers were characterized using scanning electron microscopy (SEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma optical emission spectroscopy (ICP-OES), thermogravimetric analysis (TGA), and Brunauer–Emmett–Teller (BET) surface area analysis. pH-responsive DOX release was evaluated under physiological (pH 7.4) and acidic (pH 5.0) conditions. Cytotoxicity was assessed in A549 lung cancer cells via the MTT assay. Additionally, in vitro time-lapse live-cell imaging and wound healing assays were conducted to evaluate intracellular drug uptake and cellular responses. Our findings highlight the critical influence of zinc salt selection and ligand ratio on the structure–property–function relationships of ZIF-8, providing valuable insights for the rational design of MOF-based nanocarriers in targeted cancer therapy.

Graphical Abstract

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来源期刊
Journal of Nanoparticle Research
Journal of Nanoparticle Research 工程技术-材料科学:综合
CiteScore
4.40
自引率
4.00%
发文量
198
审稿时长
3.9 months
期刊介绍: The objective of the Journal of Nanoparticle Research is to disseminate knowledge of the physical, chemical and biological phenomena and processes in structures that have at least one lengthscale ranging from molecular to approximately 100 nm (or submicron in some situations), and exhibit improved and novel properties that are a direct result of their small size. Nanoparticle research is a key component of nanoscience, nanoengineering and nanotechnology. The focus of the Journal is on the specific concepts, properties, phenomena, and processes related to particles, tubes, layers, macromolecules, clusters and other finite structures of the nanoscale size range. Synthesis, assembly, transport, reactivity, and stability of such structures are considered. Development of in-situ and ex-situ instrumentation for characterization of nanoparticles and their interfaces should be based on new principles for probing properties and phenomena not well understood at the nanometer scale. Modeling and simulation may include atom-based quantum mechanics; molecular dynamics; single-particle, multi-body and continuum based models; fractals; other methods suitable for modeling particle synthesis, assembling and interaction processes. Realization and application of systems, structures and devices with novel functions obtained via precursor nanoparticles is emphasized. Approaches may include gas-, liquid-, solid-, and vacuum-based processes, size reduction, chemical- and bio-self assembly. Contributions include utilization of nanoparticle systems for enhancing a phenomenon or process and particle assembling into hierarchical structures, as well as formulation and the administration of drugs. Synergistic approaches originating from different disciplines and technologies, and interaction between the research providers and users in this field, are encouraged.
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