Multi-spectroscopic and molecular docking analysis of tiaprofenic acid-lactoferrin binding: Implications for...

Currently, neurological disorders present complex pathological challenges that often face limitations under single-target therapies, necessitating the development of multi-functional therapeutic strategies. To address these challenges, combining potent small-molecule therapeutics with versatile macromolecular carriers provides a strategic approach to achieve synergistic therapeutic outcomes. Here, we constructed a novel lactoferrin (LF)-Tiaprofenic acid (TA) supramolecular complex and evaluated its efficacy against neuroinflammation using a multi-dimensional approach. Multi-spectroscopic analyses, surface plasmon resonance, molecular docking, and molecular dynamics simulations revealed that TA binds within the C-lobe hydrophobic cavity of LF via hydrogen bonding and hydrophobic interactions, forming a stable 1:1 complex without disrupting LF secondary structure. Functionally, TA binding enhanced LF's Fe³⁺ chelation capacity. In lipopolysaccharide (LPS)-stimulated BV2 microglia, the LF-TA complex exhibited superior anti-inflammatory effects compared with either component alone, significantly suppressing nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and downstream pro-inflammatory mediators. Collectively, the LF-TA complex integrates structural stability with iron regulation, antioxidant potential, and anti-inflammatory activity, providing a promising strategy for neuroinflammatory disorder management.