Citrate is one of the most common stabilizing molecules used for metal nanoparticles. It provides a negatively charged, relatively accessible surface that performs well in water and low-ionic-strength aqueous solutions while remaining readily displaceable by proteins and other ligands.
Citrate is a small molecule with three carboxylate groups that associate relatively weakly with gold and silver surfaces. Molecules with stronger affinity for the metal surface, including thiol-containing ligands, can displace citrate, while proteins can adsorb directly to citrate-stabilized particles under appropriate conditions. These characteristics make citrate a useful starting surface for passive bioconjugation, ligand exchange, SERS, and other applications that require access to the underlying metal surface.
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Citrate Surface Properties
- Surface charge: Negative
- Isoelectric point: < pH 2
- Displaceability: More readily displaced than tannic acid but less readily displaced than carbonate
- Salt stability: Relatively low because citrate provides electrostatic rather than steric stabilization
- Hydrodynamic size: Citrate contributes minimally to hydrodynamic diameter, so DLS diameter can remain relatively close to the TEM-measured particle diameter
- Solvent compatibility: Water and low-ionic-strength aqueous buffers
Representative source material: Trisodium citrate dihydrate (Sigma-Aldrich, 71402)
Molecular weight: Trisodium citrate dihydrate, Na3C6H5O7 · 2H2O = 294.10 g/mol; citrate, C6H5O73− = 189.10 g/mol
Why Use a Citrate Surface?
The primary advantage of citrate is its combination of colloidal stabilization and surface accessibility. Citrate provides sufficient negative charge to stabilize many metal nanoparticles in low-ionic-strength aqueous environments without creating a large steric barrier around the particle.
Because citrate associates relatively weakly with the metal surface, it can be displaced during ligand exchange or passive adsorption. Thiol-containing molecules have particularly strong affinity for gold and silver surfaces, while proteins can adsorb directly to the particle under appropriate solution conditions.
Citrate is therefore useful when the original stabilizer needs to be replaced or when direct interaction with the metal surface is part of the downstream application.
Applications
- Passive protein adsorption and bioconjugation
- Lateral flow assay development
- Ligand exchange and surface modification
- Surface-enhanced Raman spectroscopy (SERS)
- Color engineering and controlled particle interactions
For passive antibody conjugation guidance, see our Nanoparticle Conjugation Protocols and Lateral Flow Assay Development Guide.
Citrate Surface Charge & Isoelectric Point
The figure above shows representative zeta potential versus pH curves for citrate-capped 20, 40, and 80 nm gold nanoparticles. These data were generated by manual titration with HCl and NaOH followed by zeta potential measurement. Although the magnitude varies somewhat with particle size, the overall pH-dependent behavior is similar.
Citrate-capped nanoparticles have a very low isoelectric point, below approximately pH 2 in this dataset. They therefore remain negatively charged across most commonly used pH conditions.
The magnitude of the negative zeta potential increases as pH becomes more basic until approximately pH 8–9. At higher pH, the measured magnitude begins to decrease, likely because the increasing ionic content introduced during titration compresses the electrical double layer.
nanoComposix has also compared citrate-coated 40 nm gold and silver nanoparticles and observed similar overall pH-dependent zeta-potential behavior between the two metal systems. This provides a useful basis for interpreting the general behavior of citrate-coated silver nanoparticles using the gold nanoparticle data shown here.
Learn more about how pH, ionic strength, and surface chemistry influence these measurements in Zeta Potential Measurements.
Salt Stability of Citrate-Capped Nanoparticles
Citrate provides primarily electrostatic stabilization and does not create a substantial steric barrier around the nanoparticle. Increasing ionic strength can therefore reduce colloidal stability by screening surface charge and compressing the electrical double layer.
The figure above shows UV-Visible spectra of citrate-capped 40 nm gold nanoparticles exposed to increasing concentrations of sodium chloride (NaCl). Separate nanoparticle dispersions were spiked with the indicated NaCl concentrations and incubated for 10 minutes before UV-Vis measurement.
Stable 40 nm gold nanoparticles retain their characteristic plasmon resonance near 520 nm. When aggregation occurs, the primary plasmon peak decreases and extinction increases at longer wavelengths, approximately 700–1100 nm, due to plasmon coupling between neighboring particles.
In this dataset, some decrease in optical density occurs at lower NaCl concentrations, while significant destabilization becomes apparent when the salt concentration increases above approximately 20 mM NaCl.
The salt concentration at which destabilization occurs depends on particle material, size, surface chemistry, concentration, and solution conditions. nanoComposix has generally observed lower salt stability for silver nanoparticles than for comparable gold nanoparticles with the same surface chemistry.
See Salt Stability of Nanoparticles for comparisons among different nanoparticle surface chemistries.
Is citrate the right surface for your application?
Talk with our technical team about passive adsorption, ligand exchange, surface charge, colloidal stability, or selecting the right nanoparticle surface chemistry.
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