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

Abstract 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.