Tumor Microenvironment-Selective Sol–Gel Mineralization of ROS-Responsive Stretchable and Conductive Hydrogel

Cancer cell-triggered sol–gel transformation of mineralized hydrogel (PAA-MnO₂) is designed as a facile strategy for cancer detection by manipulating the mineralization process in the presence of cancer cells. The mineralization of polyacrylic acid (PAA) with calcium phosphate via carboxyl-Ca²⁺ complex is initially inhibited by the incorporation of reactive oxygen species (ROS)-sensitive manganese oxide (MnO₂) with polymer dots (PDs). In this system, the mineralization can be induced after cleaving MnO₂ into Mn²⁺ by high ROS levels in cancer cells, forming a PAA-MnO₂ mineralized hydrogel and resulting in a naked-eye system for cancer monitoring. Naked-eye monitoring of ROS-responsive sol–gel transformation is performed using a circulator device containing circulating cells to discriminate cancer (HeLa, PC-3, B16F10) from normal cells (CHO-K1). With the incorporation of PDs, PAA-MnO₂ mineralized hydrogel not only provides physical transformation (stretchability, viscosity) but also fluorescence-recovery and electroconductivity changes at different cancer-cell concentrations (10⁴–10⁶ cells mL⁻¹), including distinct strain–pressure responses that can be wirelessly monitored via smartphones. Furthermore, in vivo, experiments suggest that PAA-MnO₂ mineralized hydrogel can be formed in tumor-bearing mice owing to its excellent ROS-scavenging activity at the tumor site, as confirmed by SOD2 and gene-expression analysis. Thus, this unique approach can potentially enable simple and effective cancer detection in future point-of-care diagnostics.