The Effect of a New Glucose–Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma Cell Lines

Abstract

Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite–methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mortality, and severe side effects that impairs the quality of patients’ life. Therefore, novel targeted therapies based on the malignant cells’ common traits have become an essential treatment strategy. Glucose transporters have been found to be overexpressed in neoplastic cells, including hematologic malignancies. In this study, we biologically evaluated a novel glucose–methotrexate conjugate (Glu–MTX) in comparison to a free MTX. The research aimed to assess the effectiveness of Glu–MTX on chosen human lymphoma and leukemia cell lines. Cell cytotoxicity was verified by MTT viability test and flow cytometry. Moreover, the cell cycle and cellular uptake of Glu–MTX were evaluated. Our study reveals that conjugation of methotrexate with glucose significantly increases drug uptake and results in similar cytotoxicity of the synthesized compound. Although the finding has been confined to in vitro studies, our observations shed light on a potential therapeutic approach that increases the selectivity of chemotherapeutics and can improve leukemia and lymphoma patients’ outcomes.

Different Targeting Ligands-Mediated Drug Delivery Systems for Tumor Therapy

“…The capacity of carbohydrates to bind to specific cell surface receptors and their biocompatibility make them attractive candidates as targeting ligands for applications involving tailored delivery of medicines and genes to particular cells. This section focuses on the application of carbohydrates as targeted ligands for drug delivery in tumor therapy [31,32] (Figure 3). as monosaccharides, disaccharides, and polysaccharides [29].…”

“…This finding was further corroborated by in vivo investigations conducted on mice with breast cancer. Of utmost significance, the MTX conjugate exhibited minimal toxicity towards noncancerous cells, thereby significantly enhancing the drug’s selectivity [ 31 ].…”

A Small Sugar Molecule with Huge Potential in Targeted Cancer Therapy

“…At the same time, the MTX conjugate showed low toxicity to noncancer cells, which significantly improved the selectivity of the drug. Additionally, the uptake of glycoconjugate by tumor cells and its accumulation in the intracellular compartment are significantly more efficient compared to MTX, which may indicate facilitated transport of the glycoconjugate by targeting GLUT1 transporters, its cellular distribution and intracellular release of the active molecule [ 89 , 90 ].…”