Detection of Circulating Tumor Cells from Clinical Blood by Electrically Charged Fe3O4 Nanoparticles

Tumor metastasis has been found to be associated with circulating tumor cells (CTCs) that shed from the primary tumor and enter the circulation. The characteristics of CTCs offer highly valuable information in assessing tumor aggressiveness and predicting the subsequent growth at distant organs. Therefore, detection and isolation of CTCs can serve as an effective tool in cancer diagnosis and prognosis through liquid biopsy. As a result of extreme rarity of CTCs, however, it has been extremely challenging to sensitively detect, effectively capture, and accurately identify CTCs from clinical blood. Current CTCs detection technologies mainly rely up on either the biomarker-conjugated magnetic beads or size-sensitive microfiltration membrane with certain limitations in sensitivity. In this presentation, we report an alternative but more sensitive CTC detection approach based on the cancer cell surface charge which is metabolically regulated by glycolysis without any conventional biomarkers. Based on the well-known Warburg effect, the cross-membrane movement of lactate inevitably removes labile inorganic cations, resulting in a net of negative charge on the cancer cell surfaces. A positively charged nanoprobe is designed and engineered to bind electrostatically onto the negatively charged cancer cells for capture and isolation. Since high glycolysis capacity is a hallmark characteristic of all cancer cells, the charge-based CTC detection can apply to different cancers regardless of their phenotypes. Our preliminary results show strong binding of the positively-charged nanoprobe on the cell surfaces of multitude of cancer types while insignificant binding is observed for the negatively charged nanoprobe counterpart. Also discussed is the relationship between the cancer cell surface charge and the glycolysis capacity which is the key that dictates the CTC detection sensitivity.