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Hyaluronic acid (HA) is a glycosaminoglycan predominantly internalized by cells through membrane receptors called cluster differentiation 44 (CD44). Overexpression of CD44 has been associated with the migration, proliferation, and metastatic potential of cancer cells. The molecular weight of HA, however, seems to influence its interaction with CD44. In this context, fluorescent nanotools, such as quantum dots (QDs), can enhance our understanding of cancer biology, contributing to developing more efficient and personalized diagnostic and therapeutic procedures for this disease. QDs are semiconductor fluorescent nanocrystals with unique physicochemical properties, including high resistance to photodegradation and active surfaces that enable their conjugation with biomolecules or other nanoparticles. Herein, we developed a fluorescent nanoprobe consisting of CdTe QDs and low molecular weight HA to investigate the interaction of this glycosaminoglycan with CD44 of cancer cells. The HA was conjugated with QDs, prepared in aqueous media, through dative interaction, using about 5:1 molecular ratio (HA:QDs). The conjugation was analyzed and confirmed using zeta potential measurements, Fourier-transform infrared spectroscopy, and agarose electrophoresis. Then, the nanoprobe was incubated for 30 min with human cervical adenocarcinoma (HeLa) and human breast adenocarcinoma (MCF-7) cells, which possess high and low CD44 expression, respectively. Confocal fluorescence microscopy analyses showed a punctate pattern in the central perinuclear region of HeLa cells, indicating effective internalization of the nanoprobe. On the other hand, low labeling, primarily concentrated on the plasma membrane, was observed for MCF-7 cells, consistent with the low CD44 expression. Therefore, these initial results indicate that the developed QD-based fluorescent nanotool holds promising applications in investigating the interaction of HA with CD44 receptors across cancer cell lines with varying malignancy profiles under different conditions. Using biomolecules, such as HA, is an interesting strategy for developing innovative theranostic targeted platforms for cancer.
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