Silica nanoparticles were functionalized with immobilized molecular bait, Cibacron Blue, and a porous polymeric bis-acrylamide shell. These nanoparticles represent a new alternative to capture low molecular weight (LMW) proteins/peptides, that might be potential biomarkers. Functionalized core-shell silica nanoparticles (FCSNP) presented a size distribution of 243.9 ± 11.6 nm and an estimated surface charge of −38.1 ± 0.9 mV. The successful attachment of compounds at every stage of synthesis was evidenced by ATR-FTIR. The capture of model peptides was determined by mass spectrometry, indicating that only the peptide with a long sequence of hydrophobic amino acids (alpha zein 34-mer) interacted with the molecular bait. FCSNP excluded the high molecular weight protein (HMW), BSA, and captured LMW proteins (myoglobin and aprotinin), as evidenced by SDS-PAGE. Functionalization of nanoparticles with Cibacron Blue was crucial to capture these molecules. FCSNP were stable after twelve months of storage and maintained a capacity of 3.1–3.4 µg/mg.
