Noninvasive and Highly Multiplexed Five-Color Tumor Imaging of Multicore Near-Infrared Resonant Surface-Enhanced Raman Nanoparticles In Vivo
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Abstract
In vivo multiplexed imaging aims for noninvasive monitoring of tumors with multiple channels without excision of the tissue. While most of the preclinical imaging has provided a number of multiplexing channels up to three, Raman imaging with surface-enhanced Raman scattering (SERS) nanoparticles was suggested to offer higher multiplexing capability originating from their narrow spectral width. However, in vivo multiplexed SERS imaging is still in its infancy for multichannel visualization of tumors, which require both sufficient multiplicity and high sensitivity concurrently. Here we create multispectral palettes of gold multicore-near-infrared (NIR) resonant Raman dyes-silica shell SERS (NIR-SERRS) nanoparticle oligomers and demonstrate noninvasive and five-plex SERS imaging of the nanoparticle accumulation in tumors of living mice. We perform the five-plex ratiometric imaging of tumors by varying the administered ratio of the nanoparticles, which simulates the detection of multiple biomarkers with different expression levels in the tumor environment. Furthermore, since this method does not require the excision of tumor tissues at the imaging condition, we perform noninvasive and longitudinal imaging of the five-color nanoparticles in the tumors, which is not feasible with current ex vivo multiplexed tissue analysis platforms. Our work surpasses the multiplicity limit of previous preclinical tumor imaging methods while keeping enough sensitivity for tumor-targeted in vivo imaging and could enable the noninvasive assessment of multiple biological targets within the tumor microenvironment in living subjects.
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Condition number detects simple and multi-collinearity in a linear system of reference spectra, making it potentially useful for predicting multiplexed SERS NP quantitation robustness.
“Condition number detects simple and multi-collinearity in a linear system of reference spectra, making it potentially useful for predicting multiplexed SERS NP quantitation robustness.19,29”
From Assessment of unmixing approaches for the quantitation of SERS nanoparticles in highly multiplexed spectral images (2024) · cites this paper as [29]
Simultaneous spectral signals and increased crosstalk both contribute to ill-conditioned spectral unmixing, even with narrow Raman bands.
“Simultaneous spectral signals and increased crosstalk both contribute to ill-conditioned spectral unmixing, even with the narrow spectral bands of Raman radiation.29”
From Assessment of unmixing approaches for the quantitation of SERS nanoparticles in highly multiplexed spectral images (2024) · cites this paper as [29]
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- Authors
- Yu, J. H., Steinberg, I., Davis, R. M., Malkovskiy, A. V., Zlitni, A., Radzyminski, R. K., Jung, K. O., Chung, D. T., Curet, L. D., D’Souza, A. L., Chang, E., Rosenberg, J., Campbell, J., Frostig, H., Park, S.-M., Pratx, G., Levin, C., & Gambhir, S. S.
- Affiliations
- Stanford Medicine (US)
- Carnegie Institution for Science (US)
- Corresponding author
- Yu, Jung Ho
- Gambhir, Sanjiv S.
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-11-19
- Volume
- 15
- Issue
- 12
- Pages
- 19956-19969
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- PMC
- PMC9012519
- OpenAlex
- W3109995906
- Semantic Scholar
- cb8523dc05f56b3889cf003944f338bee1d1bdcd
- Cited by
- 67
- References
- 56
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 13 · 2023: 12 · 2022: 5 · 2021: 1
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- ACS Nano (publishedVersion)
- ChemRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Figshare (submittedVersion, cc-by-nc-nd)
- Funders
- National Cancer Institute (U54 CA199075)
- National Institutes of Health (1S10RR02678001)
- Topics
- Physical Sciences › Materials Science › Electronic, Optical and Magnetic Materials › Gold and Silver Nanoparticles Synthesis and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- surface-enhanced Raman scattering, SERS nanoparticles, silica shell, ratiometric imaging, noninvasive in vivo imaging, longitudinal tumor imaging, tumor microenvironment, biomarker detection
- MeSH terms
- Animals, Diagnostic Imaging, Gold, Neoplasms, Spectrum Analysis, Raman, Mice, Nanoparticles, Metal Nanoparticles, Tumor Microenvironment
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