Accurate Quantification and Imaging of Cellular Uptake Using Single-Particle Surface-Enhanced Raman Scattering

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Analytical Chemistry

Background:

• Understanding gold nanoparticle (NP) behavior in cells is crucial for developing NP-based sensors and therapeutics.
• Single nanoparticle imaging using surface-enhanced Raman spectroscopy (SERS) is challenging due to aggregation, signal variability, and low brightness.

Purpose of the Study:

• To develop a quantitative probe for single-particle Raman imaging in living cells.
• To assess the influence of nanoparticle shape and silica encapsulation on SERS signals.
• To establish a method for reliable subcellular distribution and stability analysis of NPs in cells.

Main Methods:

• Evaluation of single-particle SERS signals from various gold NP shapes.
• Assessment of silica encapsulation's effect on SERS signals using gap-enhanced Raman tags (GERTs).
• Validation of SERS imaging with single-particle inductively coupled mass spectrometry (spICP-MS) on cell lysates.

Main Results:

• Silica-encapsulated GERTs provide an optimized, quantifiable probe for SERS mapping in cells.
• The developed approach allows for quantitative assessment of NP uptake per voxel.
• spICP-MS confirmed the quantitative imaging results and enabled assessment of NP tag stability.

Conclusions:

• Silica-encapsulated GERTs offer a robust platform for quantitative single-particle Raman imaging in living cells.
• This method reliably determines subcellular NP distribution and stability.
• The combined SERS and spICP-MS approach advances quantitative analysis of nanomaterials in biological systems.