A Novel Multifunctional Nanowire Platform for Highly Efficient Isolation and Analysis of Circulating Tumor-Specific Markers

Abstract

Circulating tumor-specific markers are crucial to understand the molecular and cellular processes underlying cancer, and to develop therapeutic strategies for the treatment of the disease in clinical applications. Many approaches to isolate and analyze these markers have been reported. Here, we propose a straightforward method for highly efficient capture and release of exosomes and circulating tumor cells (CTCs) in a single platform with well-ordered three-dimensional (3D) architecture that is constructed using a simple electrochemical method. Conductive polypyrrole nanowires (Ppy NWs) are conjugated with monoclonal antibodies that specifically recognize marker proteins on the surface of exosomes or CTCs. In response to electrical- or glutathione (GSH)-mediated stimulation, the captured exosomes or cells can be finely controlled for retrieval from the NW platform. A surface having nano-topographic structures allows the specific recognition and capture of small-sized exosome-like vesicles (30-100 nm) by promoting topographical interactions, while physically blocking larger vesicles (i.e., microvesicles, 100-1,000 nm). In addition, vertically aligned features greatly improve cell capture efficiency after modification with desired high-binding affinity biomolecules. Notably, exosomes and CTCs can be sequentially isolated from cancer patients' blood samples using a single NW platform via modulating electrochemical and chemical cues, which clearly exhibits great potential for the diagnosis of various cancer types and for downstream analysis due to its facile, effective, and low-cost performance.