Pyrophosphate-Responsive viscoelasticity and conductive Signaling of Self-reporting hydrogel sensor for detection of cancer cells

•Pyrophosphate-responsive self-reporting hydrogel is designed for cancer detection.•Signaling of self-reporting sensor produced distinct viscoelasticity & conductivity.•Cu2+-PPi interaction triggered change in pore structure of PD-Cu2+@PAA hydrogel.•PPi-Cu2+ complexation induced fluorescence recovery in cancer cell-treated hydrogel.•Cancer cell-treated hydrogel showed irreversible pressure response than normal cell. A pyrophosphate-responsive self-reporting mineralized hydrogel sensor was designed for simple naked-eye monitoring of cancer cells. The sensor utilized physical form alteration mediated via changes in viscoelasticity, shape, stretchability, and changes in fluorescence as well as the conductivity of hydrogel. The incorporation of copper ion-immobilized polymer dots (PD-Cu2+) into the mineralized polyacrylic acid (PAA) hydrogel produced a self-reporting ability to differentiate between cancer and normal cells in response to different levels of pyrophosphate (PPi) in cancer and normal cells. The detachment of Cu in PD-Cu2+@PAA mineralized hydrogel by PPi resulted in a fluid-like, softer, and injectable hydrogel after treatment with cancer cells (HeLa, KG-1) compared to that observed in normal cells (CHO-K1) in the presence of ALP inhibitor. Furthermore, the Cu2+-PPi interaction recovered the fluorescence and decreased the conductivity of hydrogel; the resistance changes in HeLa (ΔR = 380 Ω) and KG-1-treated PD-Cu2+@PAA mineralized hydrogels (ΔR = 390 Ω) were higher than those of CHO-K1-treated PD-Cu2+@PAA mineralized hydrogel (ΔR = 80 Ω) with and without ALP inhibitor. Moreover, the wireless sensing system revealed that cancer cell-treated hydrogel showed an irreversible pressure response compared with normal cell-treated hydrogel. Thus, this self-reporting hydrogel has the potential to be applied to point-of-care cancer diagnostics.