Background

Gold nanoparticles have garnered significant attention in nanomedicine due to their unique physicochemical properties. Their small size (typically 1-100 nm), large surface-to-volume ratio, and surface plasmon resonance characteristics make them ideal candidates for drug delivery, imaging, and therapeutic applications.

Turkevich Method

The Turkevich method, first reported in 1951, remains one of the most widely used approaches for synthesizing citrate-stabilized gold nanoparticles. This method offers several advantages including simplicity, reproducibility, and the production of relatively monodisperse particles. The citrate ions serve dual roles as both reducing agent and stabilizing ligand, preventing particle aggregation.

Applications in Drug Delivery

AuNPs synthesized via this method can be functionalized with targeting ligands, therapeutic agents, and imaging probes, making them versatile platforms for theranostic applications. The biocompatibility of citrate-stabilized AuNPs has been demonstrated in numerous in vitro and in vivo studies.

Size Control Mechanisms

The size of AuNPs synthesized using the Turkevich method is primarily controlled by the citrate-to-gold ratio and reaction temperature. Higher citrate concentrations generally produce smaller particles due to faster nucleation kinetics. Our optimized protocol yields particles in the 15-20 nm range, which is ideal for passive tumor targeting via the enhanced permeability and retention (EPR) effect.

Characterization Findings

UV-Vis spectroscopy reveals a characteristic surface plasmon resonance peak at approximately 520 nm, confirming the formation of spherical gold nanoparticles. The peak position and width provide insights into particle size and dispersion. DLS measurements indicate a hydrodynamic diameter of 18 ± 2 nm with a polydispersity index (PDI) of 0.15, demonstrating excellent monodispersity. TEM images confirm the spherical morphology and allow for direct measurement of core particle size.

Stability Considerations

Citrate-stabilized AuNPs exhibit good colloidal stability at neutral pH due to electrostatic repulsion. However, stability may decrease in high ionic strength solutions or at extreme pH values. For long-term storage, keep AuNP suspensions at 4°C in the dark. Do not freeze, as this may cause irreversible aggregation.

Functionalization Potential

The citrate coating on AuNPs can be readily displaced by thiols, allowing for surface modification with targeting peptides, antibodies, or other biomolecules. This enables the development of targeted drug delivery systems with enhanced specificity for diseased tissues.

This protocol provides a reliable method for synthesizing monodisperse gold nanoparticles suitable for biomedical applications. The Turkevich method offers excellent reproducibility and scalability, making it accessible to researchers across various disciplines. The resulting AuNPs exhibit uniform size distribution, good colloidal stability, and potential for surface functionalization.

Key advantages of this protocol include: (1) simplicity and minimal equipment requirements, (2) high reproducibility with proper temperature control, (3) production of biocompatible, citrate-stabilized nanoparticles, and (4) versatility for subsequent functionalization steps.

Future directions include optimizing the protocol for different size ranges, exploring alternative stabilizing agents, and developing one-pot synthesis methods that incorporate drug loading during nanoparticle formation.