Abstract

Tumor is a leading cause of mortality worldwide, with hypoxia and elevated endogenous formaldehyde (FA) identified as two critical features of tumor microenvironment that act synergistically to promote tumor progression. Therefore, precise imaging of both hypoxia and FA in vivo is of significance for precise tumor detection. However, the development of dual-responsive probes for tumor hypoxia and endogenous FA remains a significant challenge. Herein, we developed a novel "AND" logic probe Cy-MB@F4C4A that could respond to FA and hypoxia simultaneously. A FA-responsive probe, Cy-MB, was pre-encapsulated within a hypoxia-responsive azocalixarene F4C4A via simple noncovalent strategy to construct "AND" logic probe Cy-MB@F4C4A. The fluorescence signal of the "AND" logic probe Cy-MB@F4C4A is only activated in the presence of both tumor hypoxia and endogenous FA. Therefore, the probe Cy-MB@F4C4A demonstrates remarkable stability owing to its dual-response capability. Furthermore, it demonstrates high selectivity and sensitivity for FA with a detection limit at 11.5 mu M under hypoxic conditions, rendering it suitable for detection and imaging in biological systems. More importantly, "AND" logic probe Cy-MB@F4C4A could be successfully applied for accurate tumor imaging in vitro and in vivo. We anticipate that this "AND" logic probe will offer significant potential for cancer theranostic.

Keywords Plus：MICROENVIRONMENTAL REGULATION，TUMOR MICROENVIRONMENT，CANCER，RESISTANCE，CELLS

Published in  TALANTA，Volume297；10.1016/j.talanta.2025.128632，JAN 1 2026