Aqueous-stable perovskite nanoprobes via dual-anchoring strategy for sensitive tumor-associated phospholipase D biosensing

Phospholipase D (PLD) activity plays a critical role in tumor progression, yet its highly sensitive detection remains challenging. In this study, we developed metal halide perovskite nanoprobes via a dual-anchoring strategy that employed co-encapsulation of phospholipid and cholesteryl hemisuccinate (Chs) for the sensitive and selective monitoring of PLD activity. The Chs molecule not only enhances the stability of the phospholipid membrane via its cholesterol moiety but also passivates surface defects of the perovskite through the succinate group, endowing the nanoprobes with exceptional optical properties (PLQY >90 %) and long-term aqueous stability (> 7 days). The nanoprobe operates via a turn-off fluorescence response triggered by PLD-specific hydrolysis of the phospholipid layer, achieving a low detection limit of 0.51 U/L and a wide linear range (5–2000 U/L) with good anti-interference capability. Furthermore, the nanoprobes were successfully applied to in situ imaging of PLD activity in living cells, enabling discrimination between tumor cells with different PLD expression levels. This study not only paves the way for designing novel perovskite-based probes for biomedical applications but also offers a valuable fluorescent imaging tool to monitor tumor progression.