Hydrothermal synthesis of Ag@Zn-salen MOF nanocomposite via a two-step method for ultrasensitive CA15-3 biosensing in breast cancer diagnostics

Abstract

Metal–organic frameworks (MOFs) integrated with noble metal nanoparticles offer transformative potential in biosensing, yet bimetal composites face persistent challenges, including inhomogeneous nanoparticle distribution and framework destabilization. Salen-based MOFs, prized for their thermal stability and tunable electronic properties, remain underexplored for bimetal systems despite their catalytic and plasmonic synergies. This study addresses the critical need for a synthesis strategy that ensures the uniform dispersion of plasmonic silver nanoparticles (Ag NPs) within a robust Zn-salen metal–organic framework (MOF) matrix while preserving structural integrity for biomarker detection applications. Conventional one-pot methods for bimetal MOFs often result in Ag NP aggregation (>200 nm) and pore blockage, compromising porosity and active site accessibility—key limitations for biosensor development. A hierarchical Ag@Zn-SalenMOF composite was engineered via a novel two-step hydrothermal approach: (1) Zn-salen framework assembly, followed by (2) DMF-mediated in situ reduction of AgNO₃ to submicron Ag NPs (150–200 nm). The composite was characterized by FE-SEM, HR-TEM, XPS, and XRD, and functionalized with anti-CA15-3 antibodies for biosensor fabrication. The composite exhibited exceptional thermal stability (>300 °C), uniform Ag NP distribution (189 nm avg.), and strong interfacial electronic coupling. The biosensor achieved a CA15-3 detection limit of 0.12 U mL⁻¹ (Stern–Volmer constant: 0.004 U mL⁻¹) with 93.3% sensitivity and 91.6% specificity in clinical serum samples (n = 20), outperforming conventional immunoassays. Stability studies confirmed less than 5% signal drift over 2 months, enabled by sodium azide preservation. This work addresses long-standing synthesis challenges in bimetallic metal–organic frameworks (MOFs), providing a scalable platform for ultrasensitive biomarker detection. The Ag@Zn-Salen MOF biosensor's precision, robustness, and clinical validity position it as a transformative tool for breast cancer monitoring and early diagnosis.