Synergistic in-vitro inhibition of lung cancer cells using L-carnosine-capped copper nanoclusters

Abstract

Traditional cancer treatments are often associated with high toxicity and significant side effects, limiting the safe dosage range for patients. To address these challenges, there is a critical need for specific medications with reduced toxicity and enhanced efficacy. This study combined the unique anticancer properties of L-carnosine, a dipeptide, and copper to synthesize L-carnosine-capped copper nanoclusters (Cu₄L₅). The nanoclusters were characterized using UV–vis spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, HR-TEM, HR-MS, and EDX mapping. The synthesized Cu₄L₅ exhibited synergistic anticancer effects against A549 lung cancer cells, as evidenced by MTT assay results showing significantly higher cytotoxicity toward cancer cells while demonstrating minimal toxicity to normal Vero-2 cells, as indicated by IC₅₀ values. Their anticancer properties were compared to those of L-carnosine alone and copper nanoclusters stabilized with L-histidine. Cu₄L₅ exhibited approximately twofold greater anticancer activity, confirming the enhanced efficacy of the L-carnosine-CuNCs combination. Additionally, CuNCs enable the detection of GSH in solution within the nanomolar concentration range using the Stern-Volmer equation. Computational studies of nanoclusters further revealed that copper atoms bind with ligands through its N of imidazole ring and CO group, leaving carboxylate and NH₂ sites available for interacting with cancer cells. This dual functionality of Cu₄L₅, combining therapeutic and diagnostic capabilities, highlights its potential as a promising candidate for targeted cancer treatment with minimal off-target effects.