Effective capture of circulating tumor cells from an S180-bearing mouse model using electrically charged magnetic nanoparticles

Zhiming Li,Jun Ruan,Xuan Zhuang

doi:10.1186/s12951-019-0491-1

Abstract

BackgroundTechnology enabling the separation of rare circulating tumor cells (CTCs) provides the potential to enhance our knowledge of cancer metastasis and improve the care of cancer patients. Modern detection approaches commonly depend on tumor antigens or the physical size of CTCs. However, few studies report the detection of CTCs by the electrical differences between cancer cells and normal cells.ResultsIn this study, we report a procedure for capturing CTCs from blood samples using electrically charged superparamagnetic nanoparticles (NPs). We found that only positively charged NPs attached to cancer cells, while negatively charged NPs did not. The capture method with positively charged NPs offered a sensitivity of down to 4 CTCs in 1 mL blood samples and achieved a superior capture yield (> 70%) for a high number of CTCs in blood samples (103–106 cells/mL). Following an in vitro evaluation, S180-bearing mice were employed as an in vivo model to assess the specificity and sensitivity of the capture procedure. The number of CTCs in blood from tumor-bearing mice was significantly higher than that in blood from healthy controls (on average, 75.8 ± 16.4 vs. zero CTCs/100 μL of blood, p < 0.0001), suggesting the high sensitivity and specificity of our method.ConclusionsPositively charged NPs combined with an in vivo tumor model demonstrated that CTCs can be distinguished and isolated from other blood cells based on their electrical properties.

Highlights

Technology enabling the separation of rare circulating tumor cells (CTCs) provides the potential to enhance our knowledge of cancer metastasis and improve the care of cancer patients
We found that most sarcoma 180 (S180) and MDA-MB-231 cancer cells were captured at a zeta potential of + 25 mV, while normal white blood cells (WBCs) were not (Additional file 1: Figure S1)
The results showed that the captured CTCs were double-positive (TRITC/green fluorescent protein (GFP)) and polyploidy tumor cells, which are tumor cells excreted from the primary tumors (Additional file 1: Figure S3)

Summary

Introduction

Technology enabling the separation of rare circulating tumor cells (CTCs) provides the potential to enhance our knowledge of cancer metastasis and improve the care of cancer patients. It has been accepted that CTCs constitute seeds for the tumor metastasis, which is responsible for the majority of cancer-related death. 100 years ago, Cure et al found that cancer cells have extraordinarily high concentrations of negatively charged glycoproteins on their exterior surface, which act as an electrical shield [4, 5]. Sialic acid is considered to be one of the primary molecules responsible for conferring a negative charge to glycoproteins. Since human chorionic gonadotropin (hCG) contains large amounts of sialic acid, this results in cancer cells having a stronger negative cell surface charge than normal cells [6]. Jeffrey recently observed that acute lymphoblastic lymphoma T-cells (T-ALL cells) exhibit a faradaic electrochemical response that is two orders of magnitude greater than that of normal cells [9]

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