నానోమెడిసిన్ & నానోటెక్నాలజీ జర్నల్

నైరూప్య

Accumulation and Distribution of Non-targeted and Anti-CD44-conjugated Quantum Dots in Distinct Phenotypes of Breast Cancer

Simona Steponkiene, Dominyka Dapkute, Una Riekstina and Ricardas Rotomskis

Background: It has been postulated that most if not all cancers are hierarchically organized and contain distinct phenotypes of cells. In breast tumors CD44+/CD24-/EpCAM+ phenotype had been shown to possess the properties of cancer stem-like cells, while CD44low/-/CD24+/EpCAM+ cells represent more differentiated tumor cells that are often classified as luminal subtype of cancer. Quantum dots had already been used for imaging in vitro and in vivo, however the information about accumulation and time-dependent distribution of antibody-conjugated quantum dots in different phenotypes of breast cancer is still missing. Results: The accumulation and distribution of QDs was compared between CD44low/-/CD24+/EpCAM+ (MCF-7) and CD44+/CD24-/EpCam+ (MDA-MB-231) cells. The accumulation of non-targeted QDs was twofold more efficient in CD44low/-/CD24+/EpCAM+ cells than in CD44+/CD24-/EpCam+. Conjugation of anti-CD44 to QDs minimized uptake of QDs in CD44low/-/CD24+/EpCAM+ cells thus showing the selectivity of this conjugate to CD44-positive cells. Most importantly, after 24 hours post labeling the membrane-bound anti-CD44-QDs was engulfed inside the cytoplasm of cells, while the conjugate of anti-CD44 and fluorescein isothiocyanate (FITC) remained on the cell membrane. Conclusion: The combination of QDs and antibodies gives a synergistic effect; antibody assures specific labeling of the desired cells while QDs initiate engulfment of the conjugate inside cells. Antibodies themselves are not capable of initiation of receptor-mediated endocytosis. Therefore these results are very important and might be used in the development of multifunctional agents for targeted labeling and delivery of bioactive compounds.