QUANTUM DOT-BASED FLUORESCENT NANOPROBES FOR STUDYING THE GLUCOSE UPTAKE BY CANCER CELLS AS MONOLAYERS AND SPHEROIDS

The uptake of glucose and its analogs by cancer cells is different, such as its metabolism. This phenomenon is known as the Warburg effect. Therefore, the development of fluorescent glyconanoprobes can help better understand the cancer complexity at cellular level and support improved diagnosis and therapeutics for this disease. In this context, herein, the unique physical-chemical properties of quantum dots (QDs) were explored to develop a novel fluorescent glyconanoprobe based on the 1-thio-β-D-glucose (Glc). The Glc-QDs conjugate was prepared using the affinity of the Glc thiol group by the QD semiconductor surface. Then, the biological interaction with the nanoprobe was analyzed through fluorescence microscopy and flow cytometry. For this, both monolayers and spheroids of HeLa cells were employed since spheroids have been gaining prominence for better mimics the tumor microenvironment. The hanging drop method was used to prepare the spheroids. The confirmation of the conjugation was achieved using Zeta potential () measurements, FTIR analyses, and fluorescence correlation spectroscopy. Moreover, a biological assay, based on the lectin-carbohydrate affinity, using Candida albicans yeasts coated with concanavalin A was also developed, which also confirmed the conjugation. The fluorescence microscopy analyses indicated that the glyconanoprobe was found in the cytoplasm of HeLa cells cultivated both as monolayers and spheroids. Flow cytometry assays revealed an intense cellular uptake of the glyconanoprobe, above ca. 76%, even after interaction with spheroids, applying short incubation times. Therefore, a novel fluorescent glyconanoprobe was developed, which demonstrated potential to be used as a nanotool for investigating mechanisms involved in the glucose uptake by cancer cells cultivated as simpler (monolayers) or more complex (spheroids) biological models.