Antibacterial and antioxidant activities of macluraxanthone-loaded gold nanoparticles: mechanistic insights against pathogenic bacteria

Bacterial infections and antibiotic resistance remain a major global health concern, underscoring the need for new therapies. Poor bioavailability of bioactive compounds poses challenges in successful clinical applications, rendering nanoparticle conjugation which is one of the effective strategies for overcoming. Macluraxanthone (MCX), a naturally derived compound exhibiting antioxidant and antimicrobial properties, but displayed poor bioavailability and limited antimicrobial effect against Gram-negative bacteria. Herein, MCX was conjugated with gold nanoparticles (AuNPs) to enhance its bioactivity, stability, and targeted delivery. Transmission electron microscopy (TEM) analysis confirmed the formation of spherical AuNPs with uniform distribution, while the faint halo surrounding some AuNPs–MCX particles suggested successful MCX adsorption. The synthesized AuNPs−MCX conjugates displayed a preferred particle size of 25.1 nm, providing maximum MCX release after 48 h, reaching approximately 78% at pH 7.4 and 82% at pH 5.04. Antioxidant assay indicated that MCX is a strong antioxidant agent, but its activity was impaired upon conjugation with AuNPs. Compared to the free MCX, the AuNPs−MCX conjugates exhibited considerably enhanced antimicrobial activities against Gram-negative bacteria ( E. coli , S. flexneri , V. cholerae , and S. enterica serovar Typhi) but impaired activities against Gram-positive ones ( S. aureus , MRSA, and L. monocytogenes ). Scanning electron microscope (SEM) further confirmed significant bacterial cell damage after treatment with both MCX and AuNPs−MCX, including cell wall degradation, deep pits, and cavity formation. Further investigations also revealed that the mechanisms behind the altered antimicrobial activities of AuNPs−MCX conjugates could be partly due to the changes in their abilities to produce reactive oxygen species (ROS) and eradicate biofilm. Interestingly, free MCX exhibited moderate cytotoxicity toward Vero cells (IC₅₀ = 17.12 μg/mL), whereas AuNPs–MCX showed non-cytotoxicity, indicating improved biocompatibility. These findings highlight the potential of AuNPs−MCX conjugates as an effective nanoformulation, offering selective antibacterial activity against Gram-negative pathogens.