Multifunctional Gelatin-Nanoparticle-Modified Chip for Enhanced Capture and Non-Destructive Release of Circulating Tumor Cells

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.

Progress in Gelatin as Biomaterial for Tissue Engineering

“…Entrapped cells, afterwards, are released steadily from the platform owing to the ability of gelatin to respond to physical stimuli (such as temperature). This gelatin-based platform allows for cancer cell isolation and posterior analysis as well as ensuring the encapsulated cells' viability at all times, as a result of the biocompatibility provided by this biomaterial [117,118]. This novel system that traps cells and allows analyzing them in detail is a significant breakthrough in personalized medicine, as it would allow accurate diagnosis together with specific treatments for each case of tumor.…”

Recent advances of liquid biopsy: Interdisciplinary strategies toward clinical decision‐making

“…This can be achieved through various methods, each tailored to the intrinsic properties of the substrate. 126 For instance, Guo and colleagues utilized TiO 2 nanopillar arrays coated with a gelatin film for the efficient capture and damage-free release of CTCs (Figure 4F). 121 The interaction between the cell membrane and the nanostructure substrate contributed to an impressive CTC capture rate (94.98%).…”

“…One of the most straightforward strategies for detaching CTCs from the capturing substrate involves simply degrading the substrate itself. This can be achieved through various methods, each tailored to the intrinsic properties of the substrate 126 . For instance, Guo and colleagues utilized TiO 2 nanopillar arrays coated with a gelatin film for the efficient capture and damage‐free release of CTCs (Figure 4F).…”