A multilocus-dendritic boronic acid functionalized magnetic nanoparticle for capturing circulating tumor cells in the peripheral blood of mice with metastatic breast cancer

Abstract

BackgroundDynamic fluctuation of circulating tumor cells (CTCs) can serve as an indicator of tumor progression. However, the sensitive isolation of CTCs remains extremely challenging due to their rarity and heterogeneity. Against this dilemma, dendritic boronic acid-modified magnetic nanoparticles (MNPs) were prepared in this study, and polyethyleneimine (PEI) was utilized as a scaffold to significantly increase the number of boronic acid moieties. Then the novel developed material was applied to monitor the number of CTCs in mice with metastatic breast cancer to evaluate the therapeutic effects of matrine (Mat), doxorubicin (Dox), and Mat in combination with Dox. ResultsCompared to the low binding capacity of a single boronic acid ligand, dendritic boronic acid shows enhanced sensitivity in binding to sialic acid (SA), which is overexpressed in CTCs. The results showed that the capture efficiency of this modified material could achieve 94.7% and successfully captured CTCs in blood samples from mice with metastatic breast cancer. The CTC counts were consistent with the results of the pathologic examination, demonstrating the reliability and utility of the method. SignificanceThe dendritic boronic acid nanomaterials prepared in this study showed high specificity, sensitivity, and accuracy for cancer cell capture. The approach is expected to provide new insights into cancer diagnosis, personalized therapy, and optimization of treatment regimens.