RESUMEN
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 MoS2nanoflakes 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)-MoS2conjugates 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)-MoS2conjugates assessed by flow cytometry analysis was significantly higher compared with the cellular uptake of SKM-1 nonspecific (anti-GPC3)-MoS2conjugates. Our results indicate the importance of appropriate functionalization of MoS2nanomaterials 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.
Asunto(s)
Disulfuros/química , Sistemas de Liberación de Medicamentos/métodos , Leucemia Mieloide Aguda/metabolismo , Molibdeno/química , Nanoconjugados/química , Lectina 3 Similar a Ig de Unión al Ácido Siálico/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Humanos , Microscopía Óptica no Lineal , Lectina 3 Similar a Ig de Unión al Ácido Siálico/inmunologíaRESUMEN
Essential oils (EOs) of Thymus capitatus (Th) carvacrol chemotype and Origanum vulgare (Or) thymol and carvacrol chemotype were encapsulated in biocompatible poly(ε-caprolactone) nanocapsules (NCs). These nanosystems exhibited antibacterial, antifungal, and antibiofilm activities against Staphylococcus aureus, Escherichia coli, and Candida albicans. Th-NCs and Or-NCs were more effective against all tested strains than pure EOs and at the same time were not cytotoxic on HaCaT (T0020001) human keratinocyte cell line. The genotoxic effects of EO-NCs and EOs on HaCaT were evaluated using an alkaline comet assay for the first time, revealing that Th-NCs and Or-NCs did not induce DNA damage compared with untreated control HaCaT cells in vitro after 24 h. The cells morphological changes were assessed by label-free live cell Raman imaging. This study demonstrate the ability of poly(ε-caprolactone) nanocapsules loaded with thyme and oregano EOs to reduce microbial and biofilm growth and could be an ecological alternative in the development of new antimicrobial strategies.