Abstract

Circulating tumor cells (CTCs) in cancer patients’ peripheral blood have been demonstrated to be a significant biomarker for metastasis detection, disease prognosis, and therapy response. Due to their extremely low concentrations, efficient enrichment and non-destructive release are needed. Herein, an FTO chip modified with multifunctional gelatin nanoparticles (GNPs) was designed for the specific capture and non-destructive release of CTCs. These nanoparticles share a similar dimension with the microvilli and pseudopodium of the cellular surface; thus, they can enhance adhesion to CTCs, and then GNPs can be degraded by the enzyme matrix metalloproteinase (MMP-9), gently releasing the captured cells. In addition, the transparency of the chip makes it possible for fluorescence immunoassay identification in situ under a microscope. Our chip attained a high capture efficiency of 89.27%, a release efficiency of 91.98%, and an excellent cellular viability of 96.91% when the concentration of MMP-9 was 0.2 mg/mL. Moreover, we successfully identified CTCs from cancer patients’ blood samples. This simple-to-operate, low-cost chip exhibits great potential for clinical application.

Highlights

  • In recent decades, cancer diagnostic modalities have been mostly based on serum screening and tissue biopsy

  • gelatin nanoparticles (GNPs) were synthesized on the basis of a two-step desolvation method that we have previously reported on [30]

  • In addition to investigating the release performance of cancer cell lines, we explored the release performance of monocytes in peripheral blood to evaluate capability of circulating tumor cells (CTCs) release and its viability test

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Summary

Introduction

Cancer diagnostic modalities have been mostly based on serum screening and tissue biopsy. The biomarkers in serum are not specific enough, [1]. A more accurate and non-invasive cancer diagnosis is attracting great attention. Liquid biopsy, which is quick and non-invasive, could be a potential alternative detection method for early cancer diagnosis. The biomarkers in peripheral blood, such as circulating tumor cells (CTCs), extracellular vesicles (EVs), cell-free nucleic acids (cfNAs), and tumor-educated platelets (TEPs), could be detected as tumor-associated components [2]. In regard to these biomarkers, it is difficult to separate

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