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Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS2-based nanoconjugates
Biomedical Materials ( IF 4 ) Pub Date : 2021-08-04 , DOI: 10.1088/1748-605x/ac15b1
Pavol Štefík 1 , Adriana Annušová 2, 3 , Boris Lakatoš 1 , Katarína Elefantová 1 , Lucia Čepcová 1 , Monika Hofbauerová 2 , Anna Kálosi 3 , Matej Jergel 2, 3 , Eva Majková 2, 3 , Peter Šiffalovič 2, 3
Affiliation  

Acute myeloid leukemia (AML) is a highly aggressive type of cancer caused by the uncontrolled proliferation of undifferentiated myeloblasts, affecting the bone marrow and blood. Systemic chemotherapy is considered the primary treatment strategy; unfortunately, healthy cells are also affected to a large extent, leading to severe side effects of this treatment. Targeted drug therapies are becoming increasingly popular in modern medicine, as they bypass normal tissues and cells. Two-dimensional MoS2-based nanomaterials have attracted attention in the biomedical field as promising agents for cancer diagnosis and therapy. Cancer cells typically (over)express distinctive cytoplasmic membrane-anchored or -spanning protein-based structures (e.g., receptors, enzymes) that distinguish them from healthy, non-cancerous cells. Targeting cancer cells via tumor-specific markers using MoS2-based nanocarriers loaded with labels or drugs can significantly improve specificity and reduce side effects of such treatment. SKM-1 is an established AML cell line that has been employed in various bio-research applications. However, to date, it has not been used as the subject of studies on selective cancer targeting by inorganic nanomaterials. Here, we demonstrate an efficient targeting of AML cells using MoS2 nanoflakes prepared by a facile exfoliation route and functionalized with anti-CD33 antibody that binds to CD33 receptors expressed by SKM-1 cells. Microscopic analyses by confocal laser scanning microscopy supplemented by label-free confocal Raman microscopy proved that (anti-CD33)-MoS2 conjugates were present on the cell surface and within SKM-1 cells, presumably having been internalized via CD33-mediated endocytosis. Furthermore, the cellular uptake of SKM-1 specific (anti-CD33)-MoS2 conjugates assessed by flow cytometry analysis was significantly higher compared with the cellular uptake of SKM-1 nonspecific (anti-GPC3)-MoS2 conjugates. Our results indicate the importance of appropriate functionalization of MoS2 nanomaterials by tumor-recognizing elements that significantly increase their specificity and hence suggest the utilization of MoS2-based nanomaterials in the diagnosis and therapy of AML.



中文翻译:

基于 CD33 受体特异性 MoS2 的纳米偶联物靶向急性髓细胞白血病细胞

急性髓性白血病 (AML) 是一种高度侵袭性的癌症,由未分化的成髓细胞不受控制的增殖引起,影响骨髓和血液。全身化疗被认为是主要的治疗策略;不幸的是,健康细胞也在很大程度上受到影响,导致这种治疗产生严重的副作用。靶向药物疗法在现代医学中变得越来越流行,因为它们绕过了正常的组织和细胞。二维 MoS 2基于纳米材料的纳米材料作为有前途的癌症诊断和治疗药物在生物医学领域引起了人们的关注。癌细胞通常(过度)表达独特的细胞质膜锚定或跨越蛋白质的结构(例如,受体、酶),这些结构将它们与健康的非癌细胞区分开来。使用载有标记物或药物的基于 MoS 2的纳米载体通过肿瘤特异性标记物靶向癌细胞可以显着提高特异性并减少此类治疗的副作用。SKM-1 是一种成熟的 AML 细胞系,已用于各种生物研究应用。然而,迄今为止,它还没有被用作无机纳米材料选择性靶向癌症研究的主题。在这里,我们展示了使用 MoS 2对 AML 细胞的有效靶向纳米薄片通过简便的剥离途径制备,并用与 SKM-1 细胞表达的 CD33 受体结合的抗 CD33 抗体功能化。辅以无标记共聚焦拉曼显微镜的共聚焦激光扫描显微镜的显微镜分析证明,(抗-CD33)-MoS 2共轭物存在于细胞表面和 SKM-1 细胞内,可能通过 CD33 介导的内吞作用被内化。此外,通过流式细胞术分析评估的 SKM-1 特异性(抗 CD33)-MoS 2缀合物的细胞摄取显着高于 SKM-1 非特异性(抗 GPC3)-MoS 2缀合物的细胞摄取。我们的结果表明了对 MoS 2进行适当功能化的重要性通过显着增加其特异性的肿瘤识别元素制备纳米材料,因此表明基于MoS 2的纳米材料在AML的诊断和治疗中的应用。

更新日期:2021-08-04
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