Three-dimensional conductive PEDOT:PSS-based mixed-matrix scaffolds for efficient removal of protein-bound uremic toxins and high-throughput collection of circulating tumor cells

Abstract

The troubling connection between chronic kidney disease (CKD) and cancer may result from, for example, CKD patients being exposed to a number of major risk factors for cancers (due to residual uremic toxins in the body) or cancer patients experiencing chronic kidney failure (as an adverse effect of their therapy). Herein, we report a novel three-dimensional (3D) organic bioelectronic interface (OBEI) platform for CKD treatment, by way of hemoperfusion, that can also diagnose the levels circulating tumor cells (CTCs, the precursors of metastatic cancer) at the point of care, with high-throughput collection of targeted cells. We engineered conductive poly(3,4-ethylenedioxythiophene):polystyrenesulfonate-based mixed-matrix scaffolds, prepared through freeze-drying/cross-linking, with various adsorbents, including multiwalled carbon nanotubes, graphene oxide, and chitosan, and evaluated their removal efficiency toward protein-bound uremic toxins (PBUTs) as well as their use in the isolation of targeted CTCs and white blood cells (WBCs). Upon processing with 4 h of simulated perfusion treatment, our 3D-OBEI devices provided not only a high removal rate (ca. 40 %) of p-cresol (as a model PBUT) but also average capture efficiencies of at least 80 % (cell release efficiency: ca. 90 %) for the breast cancer cell line MCF7 and for monocytic leukemia THP-1 cells spiked in 50 mL of circulatory cell culture medium. This demonstration highlights a next-generation 3D bioelectronic device platform that enhances the removal of PBUTs while facilitating the isolation and recovery of a large number of targeted CTCs and WBCs under electrical operation with an unlimited volume capacity, with a potential for use in personalized precision medicine.