Development of novel, non-toxic PEG-albumin-AuNPs to promote macrophage migration and polarization

Polyethylene glycol (PEG)-albumin functionalized gold nanoparticles (PEG-albumin-AuNPs) were synthesized via a green, one-pot reduction approach using a fruit bioflavonoid, rutin, as a reducing and stabilizing agent. PEG-albumin-AuNPs were evaluated for their immunomodulatory potential in vitro. Surface plasmon resonance analysis confirmed nanoparticle formation. Comprehensive physicochemical characterization using zeta potential, FT-IR, XRD, and TEM demonstrated enhanced colloidal stability, crystallinity, and uniform spherical morphology. The average particle size of AuNPs ranged from 5 to 20 nm and increased to 15-20 nm following PEG-albumin functionalization. A high positive zeta potential (+49.6 mV) indicated high colloidal stability suitable for long-term storage and biomedical applications. The immunomodulatory potential of PEG-albumin-AuNPs was assessed using murine macrophage (RAW 264.7) cells. MTT assay identified 75 µg/mL as the optimal non-cytotoxic concentration. NBT reduction and LDH release assays confirmed minimal toxicity. Functional analyses, including cell-sprouting and migration assays, revealed enhanced macrophage activation, indicating a shift toward an anti-inflammatory phenotype. Overall, PEG-albumin functionalization greatly enhances the physicochemical stability and biological activity of gold nanoparticles. These findings support the potential of PEG-albumin-AuNPs as biocompatible immunomodulatory nanomaterials, although further mechanistic and in vivo validation is required.