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Updated: Mar 28, 2026

Biomolecular Imaging of Cellular Uptake of Nanoparticles using Multimodal Nonlinear Optical Microscopy
Published on: May 16, 2022
C60-SIMS imaging of nanoparticles within mammalian cells
Anna N Bloom1, Hua Tian1, Nicholas Winograd1
1Department of Chemistry, The Pennsylvania State University, 104 Chemistry Building, University Park, Pennsylvania 16802.
Abstract:
To achieve successful drug delivery via nanoparticles the interactions between the nanoparticle and the chemistry of the surrounding biological environment is of central importance. A thorough understanding of these interactions is necessary in order to better elucidate information regarding drug pathways and mechanisms of action in treatment protocols. As such, it is important to identify the location of the nanoparticle, the state of its functionalization, as well as any changes in the cellular environment. The use of cluster secondary ion mass spectrometry (SIMS) using C60 (+) primary ions makes simultaneous acquisition of this information possible. Here, SIMS has been successfully used to chemically image gold nanoparticles (AuNPs) within a model, single cell system involving macrophage-like RAW 264.7 cells. The macrophage-like properties of this cell line make it extremely well-suited for cell-uptake studies. Both AuNPs and two pharmaceutical compounds, amiodarone and elacridar, were successfully imaged within a cellular system using cluster SIMS. To verify that SIMS can also be used to detect functionalization and nanoparticles simultaneously, fluorophore-functionalized AuNPs were studied as a model system. The fluorescent characteristics of these functionalized nanoparticles enabled the visual confirmation of the presence and location of the particles within the cell.
Insights
Cluster secondary ion mass spectrometry (SIMS) successfully imaged gold nanoparticles (AuNPs) and drugs within cells. This technique allows simultaneous detection of nanoparticle location, functionalization, and cellular environment changes for improved drug delivery understanding.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Analytical Chemistry
Background:
- Understanding nanoparticle-environment interactions is crucial for effective drug delivery.
- Elucidating drug pathways and mechanisms requires knowledge of nanoparticle localization and cellular changes.
- Current methods may not simultaneously provide comprehensive information on nanoparticles and their biological context.
Purpose of the Study:
- To demonstrate the utility of cluster secondary ion mass spectrometry (SIMS) for chemically imaging nanoparticles within cells.
- To assess SIMS's capability in simultaneously detecting nanoparticle location, functionalization, and associated pharmaceutical compounds.
- To evaluate SIMS for understanding nanoparticle-cell interactions in drug delivery research.
Main Methods:
- Utilized cluster SIMS with C60(+) primary ions for chemical imaging.
- Employed macrophage-like RAW 264.7 cells as a model system for nanoparticle uptake studies.
- Successfully imaged gold nanoparticles (AuNPs) and pharmaceutical compounds (amiodarone, elacridar) within cells.
- Investigated fluorophore-functionalized AuNPs to confirm simultaneous detection of functionalization and nanoparticles.
Main Results:
- Achieved simultaneous chemical imaging of AuNPs and pharmaceutical compounds within RAW 264.7 cells.
- Demonstrated the ability of cluster SIMS to detect nanoparticle location and drug presence concurrently.
- Verified that SIMS can simultaneously detect nanoparticle functionalization (using fluorophores) and the nanoparticles themselves.
- Provided a method for analyzing nanoparticle-cell interactions and drug localization.
Conclusions:
- Cluster SIMS is a powerful tool for simultaneous chemical imaging of nanoparticles, drugs, and their functionalization within a cellular environment.
- This technique enhances the understanding of nanoparticle-based drug delivery pathways and mechanisms.
- SIMS offers a valuable approach for investigating complex nanoparticle-biomolecular interactions in biological systems.

