Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS₂-based nanoconjugates

Abstract

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.

Selective Tumor Hypoxia Targeting Using M75 Antibody Conjugated Photothermally Active MoOx Nanoparticles

“…These results are consistent with our previous findings that M75 antibody conjugated nanoplatforms are preferentially transported to organelles after 24 h of incubation . Nevertheless, in the case of the MoO x -M75 conjugates, we observed a relatively lower number of cells exhibiting lipoprotein aggregates compared with MoS 2 - or graphene oxide-based M75 conjugates. , An example of such structures can be seen in (ii) in Figure d, marked by orange color. The corresponding Raman spectra are shown in Figure S15.…”

“…Prior to cluster analysis, Principal Component Analysis (PCA) can be performed to reduce the dimensionality and lower the hyperspectral data noise. In our previous studies, we successfully visualized MoS 2 - , and GO-based , nanoflakes inside cellular matter using this method. The conjugates were localized in lysosome-rich cellular regions.…”

“…cm −1 . In our previous work, the positions of the individual molecular vibrations were described in detail, see S ̌tefi ́k et al 85 Briefly, organelles, opposite the intracellular matrix, are characterized by an inverse intensity ratio between the peaks at 1582 (pyrimidine ring vibrational mode of adenine and guanine) and 1653 rel. cm −1 (amide I vibration in proteins and the lipid C�C stretching mode).…”

“… 9 Nevertheless, in the case of the MoO x -M75 conjugates, we observed a relatively lower number of cells exhibiting lipoprotein aggregates compared with MoS 2 - or graphene oxide-based M75 conjugates. 10 , 85 An example of such structures can be seen in (ii) in Figure 5 d, marked by orange color. The corresponding Raman spectra are shown in Figure S15 .…”

Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia

“…Acute myeloid leukemia (AML) is the commonest leukemia that affects both adults and pediatrics. It is a haematological neoplasm that is characterized by uncontrolled proliferation and differentiation of hematopoietic precursor cells, which results in increased number of immature myeloblasts in the bone marrow (BM) and the peripheral blood (BP) of the patients [ 1 , 2 ]. In 2021, the American Cancer Society reported that AML was the second most commonly diagnosed leukemia and it was the leading cause of leukemia-related death in the United States [ 3 ].…”