Cancer microenvironment-recognizable negative–positive electronic signal-based pore size-tunable pH/ROS-responsive hydrogel sensor

A pH- and reactive oxygen species (ROS)-induced distinguishable negative–positive electronic signal based on porosity-tunable electroconductive hydrogel sensor was designed by incorporating diselenide-crosslinked carbon dot (dsCD)-loaded zwitterionic polymer dots (PDs) into the hydrogel for cancer detection. The dsCD@PD hydrogel sensor exhibited changes in pore size in the presence of ROS and acidic pH of cancer cells owing to diselenide bond cleavage in dsCDs and release of zwitterionic PDs. This resulted in distinct conductivity and negative gauge factor of dsCD@PD hydrogel in the presence of cancer cells and positive gauge factor in the presence of normal cells. Under application of strain and pressure, dsCD@PD hydrogel produced negative gauge factor toward cancer cells (HeLa, SNU-C2A, B16F10GFP), which was distinguishable from positive gauge factor obtained for normal cells (CHO-K1), even with only limited contact, such as handwriting movement. In vivo studies, including immunohistochemical analysis (SOD2, MMP9), showed that dsCD@PD hydrogel could effectively detect ROS and acidic pH of cancer with significant responses in the middle area of cancer, as this region exhibits higher ROS and acidic pH. Moreover, electrical signals from cancer detection could be obtained via smartphones by utilizing wireless sensing system. Thus, this hydrogel sensor possesses potential for cancer point-of-care diagnostics.