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• Copper peroxide nanodot was utilized as signal nanoprobe for photoelectrochemical sensor. • The nanodots were encapsulated in metal-organic frameworks. • The nanoprobe can self-supply H 2 O 2 by encapsulated CPNs under acidic condition. • The produced H 2 O 2 can help generate insoluble precipitation onto sensor surface. • The formed precipitation resulted in decrease of photoelectrochemical current intensity. Signal nanoprobe based on copper peroxide nanodots (CPNs) embedded within metal–organic frameworks (ZIF-8) was applied for developing photoelectrochemical (PEC) sensor for detection of circulation tumor cells (CTC). The nanoprobe can self-supply H 2 O 2 by encapsulated CPNs under acidic condition. The produced H 2 O 2 can help generate insoluble precipitation onto sensor surface in the presence of horseradish peroxidase (HRP), leading to suppressed PEC current intensity. MCF-7 was selected as model CTC, which was enriched and separated from samples by antibody modified magnetic beads (MB). Organic semiconductor BTA-C4Ph and PM6 were chosen to form n-p heterojunction on sensor surface with enhanced PEC current intensity. The PEC sensor was constructed based on "sandwich" protocol, which has a linear range from 5 cell/mL to 100 cell/mL and a limit of detection (LOD) of 3 cell/mL (S/N = 3) for MCF-7. What more, the sensor was successfully applied for detection of MCF-7 in whole blood samples. [ABSTRACT FROM AUTHOR]