Metal-mediated Fe3O4@polydopamine-aptamer capture nanoprobe coupling multifunctional MXene@Au@Pt nanozyme for direct and portable photothermal analysis of circulating breast cancer cells

Breast cancer (BC) is the most common cancer in the world and circulating tumor cells (CTCs) are reliable biomarkers for early breast cancer diagnosis in a non-invasive manner. However, effective isolation and sensitive detection of BC-CTCs by portable devices in human blood samples are extremely challenging. Herein, we proposed a highly sensitive and portable photothermal cytosensor for direct capture and quantification of BC-CTCs. To achieve efficient isolation of BC-CTCs, aptamer functionalized Fe3O4@PDA nanoprobe was facilely prepared through Ca2+-mediated DNA adsorption. To further detect the captured BC-CTCs with high sensitivity, multifunctional two-dimensional Ti3C2@Au@Pt nanozyme was synthesized, which not only possessed superior photothermal effect but also exhibited high peroxidase-like activity for catalyzing 3,3′,5,5′-tetramethylbenzidine (TMB) to produce TMB oxide (oxTMB) with a strong photothermal characteristic, combining with Ti3C2@Au@Pt to synergistically amplify the temperature signal. Moreover, numerous Ti3C2@Au@Pt nanocomposites would be selectively attained on the BC-CTCs surface through multi-aptamer recognition and binding strategy, which further enhanced the specificity and facilitated signal amplification. Therefore, direct separation and highly sensitive detection of BC-CTCs was successfully achieved in human blood samples. More significantly, the controlled release of the captured BC-CTCs without affecting cell viability could be straightforwardly realized by a simple strand displacement reaction. Thus, with the distinct features of portability, high sensitivity, and easy operation, the current method holds great promise for early diagnosis of breast cancer.