Quercetin-Coated Silver and Gold Nanoparticles Show Antioxidant and Cell-Line Activity in Lab Study

Researchers in India have reported a one-pot, sunlight-driven method for making quercetin-functionalized silver and gold nanoparticles, in which the plant flavonoid quercetin acts simultaneously as the reducing agent that converts metal ions into metal nanoparticles and as the capping agent that stabilizes them. The study, published in Gold Bulletin, describes the synthesis, characterization, and preliminary laboratory evaluation of these two nanomaterials, which the authors tested for antioxidant, antibacterial, and anticancer-associated activity in cell-based and computational assays.

The synthesis itself is strikingly simple. The team dissolved 3 milligrams of quercetin in 100 milliliters of deionized water, sonicated the solution for five minutes, and then added 1 milliliter of a 1 millimolar aqueous solution of either silver nitrate or chloroauric acid. The mixture was then exposed to sunlight for roughly five minutes. The gold nanoparticle solution turned purple, while the silver nanoparticle solution turned brown, visual cues that the researchers interpreted as signs of nanoparticle formation. Quercetin was chosen because earlier work suggested it can donate electrons through its hydroxyl and carbonyl groups, reducing silver and gold ions to metallic nanoparticles while capping their surfaces to prevent aggregation. The authors note that the precise mechanism by which sunlight accelerates the reaction remains an open question, with the working hypothesis being that photonic excitation of the metal ions increases their reactivity.

Characterization relied on a battery of complementary techniques. Ultraviolet-visible spectroscopy showed a localized surface plasmon resonance peak at 520 nanometers for the gold conjugates and 430 nanometers for the silver conjugates, with single peaks suggesting relatively uniform particle populations. Fourier transform infrared spectroscopy indicated that the O–H, C=O, and C–O bands prominent in free quercetin were attenuated or absent in the conjugates, consistent with the involvement of those functional groups in reducing and stabilizing the metal cores. Field emission gun transmission electron microscopy and nanoparticle tracking analysis independently yielded average diameters of approximately 28 nanometers for the gold particles and 32 nanometers for the silver particles, with a predominantly spherical morphology. High-performance liquid chromatography showed that the quercetin retention peak became nearly flat after synthesis, which the authors took as evidence that quercetin had been consumed in reducing the metal ions.

The antioxidant evaluation used the DPPH radical scavenging assay, a standard spectrophotometric test in which a stable free radical loses its deep purple color when reduced by an antioxidant. Quercetin-functionalized silver nanoparticles performed best, with a reported IC50 of 10.00 micrograms per milliliter, matching the ascorbic acid standard used as a positive control and far outperforming both the gold conjugates, which showed an IC50 of 80.0 micrograms per milliliter, and free quercetin. The authors attribute the silver conjugates’ performance to the high surface-to-volume ratio of the small particles, which they argue facilitates electron donation to free radicals. Interestingly, the data also showed a non-monotonic trend: the silver conjugates exhibited lower activity at the highest tested concentration, and the gold conjugates showed reduced activity at 40 micrograms per milliliter compared with lower doses. The authors suggest possible explanations including nanoparticle aggregation at high concentrations, saturation effects, interference from capping molecules, or even pro-oxidant behavior generating reactive oxygen species at elevated doses.

Antibacterial activity was assessed by the agar disk diffusion method against four bacterial strains: the Gram-positive Staphylococcus aureus NCTC 8325 and Bacillus subtilis QST 713, and the Gram-negative Salmonella typhi CT18 and Escherichia coli ATCC 27853. Each test compound was applied at 30 micrograms per milliliter, with chloramphenicol as the positive control. The silver conjugates produced the largest inhibition zones among the quercetin-based materials: 15 plus-or-minus 1 millimeter against S. aureus, 13 plus-or-minus 2 millimeters against S. typhi, 9 plus-or-minus 2 millimeters against E. coli, and 6 plus-or-minus 1 millimeter against B. subtilis. The gold conjugates produced zones of 9, 11, 10, and 12 millimeters against the same organisms in that order, while free quercetin showed minimal activity, ranging from 1 to 5 millimeters. Chloramphenicol, as expected for a clinical antibiotic, was substantially more effective, with zones of 30 to 47 millimeters. The authors propose that the nanoparticle formulation improves quercetin’s solubility and interaction with bacterial membranes and may promote leakage of intracellular contents, though these mechanisms remain to be directly demonstrated.

The computational arm of the study used molecular docking in AutoDock Vina against a receptor protein derived from the crystal structure with PDB ID 1NKP. The team docked quercetin alone, clusters of eight gold atoms, and clusters of eight silver atoms, both individually and as combined quercetin-metal complexes. The calculated binding free energies ranked the silver conjugate most favorably at minus 8.27 kilocalories per mole, followed by quercetin alone at minus 7.3 kilocalories per mole, with the gold conjugate least favorable at minus 4.15 kilocalories per mole. The docking analysis also detailed differences in hydrogen bonding, electrostatic, and van der Waals interaction patterns among the three ligand forms, with the silver conjugate showing stronger polar interactions with specific arginine residues. These are computational predictions about binding geometry and energy, not measurements of biological effect, and their relevance to the observed in vitro activity has not been established experimentally.

The anticancer-associated evaluation used the sulforhodamine B colorimetric assay, which quantifies cellular protein mass as a proxy for cell number, against two human cancer cell lines: SiHa cervical cancer cells and HT-29 colon cancer cells. Compounds were tested at concentrations from 10 to 80 micrograms per milliliter over 24 hours, with the chemotherapy drug adriamycin as a positive control. In the SiHa line, the reported GI50, the concentration inhibiting net protein growth by 50 percent, was 22.7 micrograms per milliliter for the quercetin-silver conjugates, compared with 75.7 micrograms per milliliter for free quercetin and less than 10 micrograms per milliliter for adriamycin. The quercetin-gold conjugates did not reach a measurable GI50 in SiHa cells within the tested range. In the HT-29 line, the reported GI50 values were not evaluable for quercetin and the silver conjugates within the tested range, while the gold conjugates and adriamycin both showed GI50 values below 10 micrograms per milliliter. The authors also report dose-dependent growth inhibition curves, with the gold conjugates peaking at higher inhibition values in HT-29 cells at the 80 micrograms per milliliter dose.

The picture across the cytotoxicity data is more nuanced than the abstract’s summary suggests. The authors state in their discussion that the silver conjugates showed the highest cytotoxic efficacy, with reported LC50 values of 80 micrograms per milliliter for free quercetin, 40 micrograms per milliliter for the gold conjugates, and 20 micrograms per milliliter for the silver conjugates, and they attribute this to enhanced cellular uptake, reactive oxygen species generation, and oxidative stress triggering apoptotic pathways. Yet their own tabulated GI50 and TGI values lead them to conclude elsewhere that the gold conjugates emerged as the most promising candidate across both cell lines due to dose-dependent activity, and they note that the silver conjugates lost activity at higher doses in SiHa cells, possibly due to aggregation. Readers should treat these internal inconsistencies as a caveat: the relative ranking of the two nanomaterials depends on which endpoint and cell line is considered.

It is important to emphasize the scope of these findings. All biological results come from in vitro assays: a cell-free radical scavenging test, disk diffusion on bacterial cultures, and short-term exposures of two immortalized cancer cell lines. No animal studies, no normal-cell toxicity controls, and no clinical data are reported, so none of these results can be extrapolated to therapeutic benefit in humans. Adriamycin outperformed both nanomaterials in SiHa cells, and the reported activity of the conjugates against HT-29 cells was comparable to or weaker than the standard drug depending on the metric. The docking results are model-based predictions. The authors themselves frame the work as positioning quercetin-functionalized metal nanoparticles as a promising avenue for further cancer research and therapeutic development, not as an established therapy.

Within those limits, the study offers a concrete demonstration that a common dietary flavonoid can serve double duty as both reducer and stabilizer in a rapid, low-cost, binder-free nanoparticle synthesis, and that the resulting particles differ measurably from free quercetin in antioxidant, antibacterial, and cell-line assays. The authors suggest future work on optimizing stability, targeting, and drug-delivery applications, and on elucidating the sunlight-driven reduction mechanism. Whether quercetin-coated silver or gold nanoparticles can translate from the bench toward any biomedical use will depend on addressing toxicity, biodistribution, and the dose-dependent anomalies the authors themselves observed.

Subject of Research: Green synthesis and in vitro evaluation of quercetin-functionalized silver and gold nanoparticles

Article Title: Integrated synthesis and characterization of quercetin-functionalized silver and gold nanoparticles: exploring antioxidant, antibacterial, and anticancer properties through in silico and in vitro studies

Article References: Sah, P. M., Naik, H. S., Kalra, P., Raut, R. W., Lakkakula, J., Barage, S., & Uddin, I. (2025). Integrated synthesis and characterization of quercetin-functionalized silver and gold nanoparticles: exploring antioxidant, antibacterial, and anticancer properties through in silico and in vitro studies. Gold Bulletin, 58(2), Article 12. https://doi.org/10.1007/s13404-025-00366-w

Image Credits: AI Generated

DOI: 10.1007/s13404-025-00366-w

Keywords: quercetin, silver nanoparticles, gold nanoparticles, green synthesis, antioxidant, antibacterial, DPPH assay, SRB assay, SiHa, HT-29, molecular docking, nanomedicine