Host Institution:
Koç University Translational Medicine Research Center (KUTTAM)
Supervisor:
Safacan Kölemen, PhD
Co-Supervisor:
Devrim Gözüaçık, PhD
Project Name:
Targeted Nanoparticle Delivery of Sialyltransferase Inhibitors for the Treatment of Multiple Myeloma Cancer Cells
Project Summary:
Aberrant glycosylation has long been known to be a characteristic of cancer, since it affects various facets of tumour biology. Among the several glycosylation processes, cancer frequently exhibits dysregulation of sialylation—the addition of sialic acid to underlying oligosaccharides. Many cancers, including multiple myeloma, have increased expression of sialylated glycans, which is frequently associated with aggressive metastatic behaviour. Plasma cell cancer, known as myeloma, begins in the bone marrow and spreads to many parts of the skeleton, including the skull. The bone marrow is a crucial niche in myeloma, providing the cancerous cells with a supportive microenvironment and shielding them from chemotherapy. The removal of sialic acid from tumour and stromal cells can significantly boost anti-tumor immune responses by preventing cancer cell spread, overcoming medication resistance, and enhancing the efficacy of immunotherapy. The previous results lower hypersialylation by inhibiting key enzymes involved in the process with a medication known as a sialyltransferase inhibitor. When this medication was administered directly into tumours in mice, it produced significant anti-tumor responses as well as evidence of immune system reactivation. However, when given in large amounts directly into the bloodstream, this medication causes kidney damage. Nanoscale coordination polymers have recently demonstrated great potential in the biomedical field due to their unique advantages, such as their inherent biodegradability, a mesoporous structure that can load a variety of therapeutic or imaging molecules, and diverse components in both metal ions and organic ligands to render them versatile functionalities in a single system. We intend to circumvent this by delivering the sialyltransferase inhibitor specifically into the tumor.