Self-Assembled EGCG@Zn Fluorescent Nanocomplexes for Sensitive Detection of Amyloid-β₄₂

Amyloid-β₄₂ (Aβ₄₂) is an important pathological biomarker associated with the development and progression of Alzheimer's disease (AD). Differentiating Aβ₄₂ species with distinct aggregation states is therefore relevant for investigating disease-associated aggregation and developing fluorescence-based sensing strategies. In this study, biocompatible EGCG@Zn fluorescent nanocomplexes were prepared through a facile coordination-driven self-assembly approach under different pH conditions and evaluated for Aβ₄₂ detection. The nanocomplexes were characterized by fluorescence spectroscopy, FE-SEM, EDX, TEM, DLS, XRD, FTIR, and XPS, confirming Zn²⁺ incorporation into the EGCG framework and the formation of nanoscale metal-phenolic assemblies with distinct morphological, structural, and surface-chemical characteristics. Their fluorescence behavior was strongly dependent on the synthesis pH, with the nanocomplex prepared at pH 7.3 exhibiting the highest intrinsic fluorescence and the most balanced analytical performance. The optimized nanocomplex produced concentration-dependent and distinguishable fluorescence responses toward the prepared oligomer-enriched and fibril-enriched Aβ₄₂ fractions. The calculated limits of detection were 9.03 × 10⁻¹² mg mL⁻¹ for the oligomer-enriched fraction and 8.02 × 10⁻¹² mg mL⁻¹ for the fibril-enriched fraction, with corresponding limits of quantification of approximately 6.3 × 10⁻¹¹ and 3.9 × 10⁻¹¹ mg mL⁻¹, respectively. In vitro evaluation using PC12 cells further demonstrated low cytotoxicity and good biocompatibility over the investigated concentration range. Overall, the self-assembled EGCG@Zn nanocomplexes provide a simple, biocompatible, and responsive fluorescent platform for proof-of-concept sensing of Aβ₄₂ aggregate-enriched fractions, with potential for further development in Alzheimer's disease biomarker analysis.