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To address this, here we report the synthesis of cysteine\u2010capped copper nanoclusters (Cys\u2010Cu NCs) in just 30 min under ambient aqueous conditions. The incorporation of <jats:italic>\u03b3<\/jats:italic>\u2010cyclodextrin (<jats:italic>\u03b3<\/jats:italic>\u2010CD) enhanced the stability and immediately amplified the photoluminescence of the nanoclusters by triggering aggregation\u2010induced emission (AIE), increasing their quantum yield from 0.15 to 0.24. The remarkable photoluminescence of <jats:italic>\u03b3<\/jats:italic>\u2010CD\u2010assisted Cys\u2010Cu NCs (<jats:italic>\u03b3<\/jats:italic>\u2010CD\u2010Cys\u2010Cu NCs) was selectively quenched by protoporphyrin IX (PPIX), enabling ultrasensitive detection with an exceptionally low limit of 70 pM. Stern\u2013Volmer analysis revealed the underlying interaction mechanisms between <jats:italic>\u03b3<\/jats:italic>\u2010CD\u2010Cys\u2010Cu NCs and PPIX. This precise detection of PPIX is critical for diagnosing and monitoring porphyrias and other heme\u2010related 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\u201310\u00a0\u00b5M), highlighting its applicability in real\u2010world systems. Additionally, the nanoclusters exhibited strong sensitivity to reactive oxygen species (ROS), underscoring their potential for oxidative stress monitoring. These findings position <jats:italic>\u03b3<\/jats:italic>\u2010CD\u2010Cys\u2010Cu NCs as a versatile, cost\u2010effective, diagnostic tool for clinical and biomedical applications.<\/jats:p>","DOI":"10.1002\/asia.202500169","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T07:21:36Z","timestamp":1747380096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cyclodextrin\u2010Assisted <scp>l<\/scp>\u2010Cysteine\u2010Capped Copper Nanoclusters: Rapid Synthesis, Enhanced Photoluminescence, and Small Molecule Interactions in Complex Biological Matrices"],"prefix":"10.1002","volume":"20","author":[{"given":"Kavya","family":"P.","sequence":"first","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Palakkad  Palakkad Kerala 678 623 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