A novel ATBH-modified gold nanoparticle for colorimetric detection and release monitoring of insulin across a wide concentration range

The visualization of insulin release can enhance patients' understanding of treatment progress and enable timely interventions, making it ideal for transdermal delivery systems. Current colorimetric methods for monitoring insulin are limited to ng mL⁻¹ levels, insufficient for real-time release monitoring. This study proposes a novel small-molecule-modified gold nanoparticle (AuNP) using surface plasmon resonance for high-concentration insulin detection and monitoring. Molecular docking identified 2-amino-4-(trifluoromethyl)benzenethiol (ATBH), a high-affinity insulin binder (−4.8 kcal mol⁻¹) featuring an amino group that reduces electrostatic repulsion between AuNPs and insulin, thereby enhancing insulin adsorption. ATBH-modified AuNPs (ATBH@AuNPs) were synthesized via Au–S bonds and characterized by SEM, TEM, UV-Vis spectroscopy, DLS, and insulin release assays. Experiments confirmed that ATBH@AuNP significantly broadens the insulin detection range from 0.35–1.4 μg mL⁻¹ to 9.87–2510 μg mL⁻¹, a 1792-fold improvement over unmodified AuNPs. A freeze-crosslinked polyvinyl alcohol (PVA) macrovesicle encapsulating ATBH@AuNP and insulin was developed, enabling real-time monitoring of insulin release through color changes caused by ATBH@AuNP aggregation.