In this report, we synthesized cysteine-capped copper nanoclusters (Cys-Cu NCs) in 30 min under ambient conditions. The inclusion of γ-Cyclodextrin (γ-CD) enhanced their stability and photoluminescence via aggregation-induced emission. The γ-CD-Cys-Cu NCs enabled ultrasensitive protoporphyrin IX (PPIX) detection (limit: 70 pM), crucial for diagnosing heme-related disorders. The method showed excellent PPIX recovery in complex biological samples such as serum and artificial urine, and high sensitivity to reactive oxygen species, indicating strong potential for biomedical applications.

Abstract

The rapid synthesis of stable copper nanoclusters has long been challenging. To address this, here we report the synthesis of cysteine-capped copper nanoclusters (Cys-Cu NCs) in just 30 min under ambient aqueous conditions. The incorporation of γ-cyclodextrin (γ-CD) enhanced the stability and immediately amplified the photoluminescence of the nanoclusters by triggering aggregation-induced emission (AIE), increasing their quantum yield from 0.15 to 0.24. The remarkable photoluminescence of γ-CD-assisted Cys-Cu NCs (γ-CD-Cys-Cu NCs) was selectively quenched by protoporphyrin IX (PPIX), enabling ultrasensitive detection with an exceptionally low limit of 70 pM. Stern–Volmer analysis revealed the underlying interaction mechanisms between γ-CD-Cys-Cu NCs and PPIX. This precise detection of PPIX is critical for diagnosing and monitoring porphyrias and other heme-related disorders. The method demonstrated excellent PPIX recovery in complex biological matrices, such as human serum and artificial urine, across a broad PPIX concentration range (0.5–10 µM), highlighting its applicability in real-world systems. Additionally, the nanoclusters exhibited strong sensitivity to reactive oxygen species (ROS), underscoring their potential for oxidative stress monitoring. These findings position γ-CD-Cys-Cu NCs as a versatile, cost-effective, diagnostic tool for clinical and biomedical applications.