Duran Mustafa, Kaga Elif
Afyonkarahisar Health Sciences University Faculty of Medicine, Department of Internal Medicine, Hematology, Afyonkarahisar, Türkiye.
Afyonkarahisar Health Sciences University Department of Medical Services and Techniques, Afyonkarahisar, Türkiye.
Cancer Manag Res. 2024 Dec 11;16:1775-1792. doi: 10.2147/CMAR.S491805. eCollection 2024.
Myeloid leukemia is a stem cell disease with high mortality due to the challenges of high-dose treatments and side effects. Innovative nanoparticle drug delivery systems are being explored to enhance efficacy and tissue-targeted therapy. This study investigates the potential of Bentonite (BNT)-based nanoparticles (NPs) as drug carriers for azacitidine (AZA) in treating THP-1 and K562 myeloid leukemia (AML) cell lines, aiming to improve drug stability, bioavailability, and therapeutic efficacy while ensuring controlled release.
Bentonite clay morphology was analyzed using Scanning Electron Microscopes. The BNT-AZA combination was tested in THP-1 and K562 cell cultures via in vitro proliferation tests, CCK-8 assays, and drug release tests with dialysis membranes. Apoptosis and internalization were evaluated using Annexin V-FITC and fluorescence methods, respectively.
The BNT-AZA exhibited controlled release over 8 hours, with 50% released within 2 hours, 90% by the 4th hour, and prolonged release beyond 8 hours. This profile reduces side effects while increasing efficacy in target cells. Bentonite demonstrated significant drug-loading capacity, controlled release, and tumor-targeting capabilities. At concentrations of 10, 25, 50, and 100 µg/mL, BNT showed dose-dependent antiproliferative effects, maintaining low cytotoxicity at lower concentrations. The combination of azacytidine and bentonite exhibited a synergistic effect in inhibiting cell proliferation, with significant decreases in cell viability in the 1 µM azacytidine + 10 µg/mL bentonite, 5 µM azacytidine + 10 µg/mL bentonite, and 10 µM azacytidine + 10 µg/mL bentonite groups compared to the controls. The combination of 1 µM AZA with 10 µg/mL BNT achieved similar efficacy to 10 µM AZA alone, suggesting a potential for dose reduction and improved safety.
BNT nanoparticles are promising carriers for AZA, enhancing targeted delivery, reducing side effects, and potentially lowering the required dose for leukemia treatment. These findings support further investigation into the clinical application of BNT-AZA in hematologic cancers.
髓系白血病是一种干细胞疾病，由于高剂量治疗的挑战和副作用，死亡率很高。目前正在探索创新的纳米颗粒药物递送系统，以提高疗效和组织靶向治疗效果。本研究调查了基于膨润土（BNT）的纳米颗粒（NPs）作为阿扎胞苷（AZA）的药物载体在治疗THP-1和K562髓系白血病（AML）细胞系中的潜力，旨在提高药物稳定性、生物利用度和治疗效果，同时确保药物控释。
使用扫描电子显微镜分析膨润土的形态。通过体外增殖试验、CCK-8测定以及使用透析膜的药物释放试验，在THP-1和K562细胞培养物中测试BNT-AZA组合。分别使用膜联蛋白V-FITC和荧光方法评估细胞凋亡和内化情况。
BNT-AZA在8小时内实现控释，2小时内释放50%，4小时内释放90%，并在8小时后持续释放。这种释放模式减少了副作用，同时提高了对靶细胞的疗效。膨润土显示出显著的载药能力、控释能力和肿瘤靶向能力。在10、25、50和100μg/mL的浓度下，BNT显示出剂量依赖性的抗增殖作用，在较低浓度下保持低细胞毒性。阿扎胞苷和膨润土的组合在抑制细胞增殖方面表现出协同作用，与对照组相比，1μM阿扎胞苷+10μg/mL膨润土、5μM阿扎胞苷+10μg/mL膨润土和10μM阿扎胞苷+10μg/mL膨润土组的细胞活力显著降低。1μM AZA与10μg/mL BNT的组合实现了与单独使用10μM AZA相似的疗效，表明有可能降低剂量并提高安全性。
BNT纳米颗粒是AZA有前景的载体，可增强靶向递送、减少副作用，并可能降低白血病治疗所需的剂量。这些发现支持进一步研究BNT-AZA在血液系统癌症中的临床应用。
