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Published on: March 17, 2023
Shortwave infrared emitting multicolored nanoprobes for biomarker-specific cancer imaging in vivo
Harini Kantamneni1, Shravani Barkund2, Michael Donzanti2
1Department of Chemical & Biochemical Engineering, Rutgers University, 98 Brett Road, Piscataway, NJ, 08854, USA.
Background:
The ability to detect tumor-specific biomarkers in real-time using optical imaging plays a critical role in preclinical studies aimed at evaluating drug safety and treatment response. In this study, we engineered an imaging platform capable of targeting different tumor biomarkers using a multi-colored library of nanoprobes. These probes contain rare-earth elements that emit light in the short-wave infrared (SWIR) wavelength region (900-1700 nm), which exhibits reduced absorption and scattering compared to visible and NIR, and are rendered biocompatible by encapsulation in human serum albumin. The spectrally distinct emissions of the holmium (Ho), erbium (Er), and thulium (Tm) cations that constitute the cores of these nanoprobes make them attractive candidates for optical molecular imaging of multiple disease biomarkers.
Methods:
SWIR-emitting rare-earth-doped albumin nanocomposites (ReANCs) were synthesized using controlled coacervation, with visible light-emitting fluorophores additionally incorporated during the crosslinking phase for validation purposes. Specifically, HoANCs, ErANCs, and TmANCs were co-labeled with rhodamine-B, FITC, and Alexa Fluor 647 dyes respectively. These Rh-HoANCs, FITC-ErANCs, and 647-TmANCs were further conjugated with the targeting ligands daidzein, AMD3100, and folic acid respectively. Binding specificities of each nanoprobe to distinct cellular subsets were established by in vitro uptake studies. Quantitative whole-body SWIR imaging of subcutaneous tumor bearing mice was used to validate the in vivo targeting ability of these nanoprobes.
Results:
Each of the three ligand-functionalized nanoprobes showed significantly higher uptake in the targeted cell line compared to untargeted probes. Increased accumulation of tumor-specific nanoprobes was also measured relative to untargeted probes in subcutaneous tumor models of breast (4175 and MCF-7) and ovarian cancer (SKOV3). Preferential accumulation of tumor-specific nanoprobes was also observed in tumors overexpressing targeted biomarkers in mice bearing molecularly-distinct bilateral subcutaneous tumors, as evidenced by significantly higher signal intensities on SWIR imaging.
Conclusions:
The results from this study show that tumors can be detected in vivo using a set of targeted multispectral SWIR-emitting nanoprobes. Significantly, these nanoprobes enabled imaging of biomarkers in mice bearing bilateral tumors with distinct molecular phenotypes. The findings from this study provide a foundation for optical molecular imaging of heterogeneous tumors and for studying the response of these complex lesions to targeted therapy.
Insights
New multispectral short-wave infrared (SWIR) nanoprobes detect multiple tumor biomarkers in vivo. These targeted probes enable optical molecular imaging of heterogeneous tumors and assessment of treatment response.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Molecular Biology
Background:
- Real-time optical imaging of tumor biomarkers is crucial for evaluating drug safety and treatment response in preclinical studies.
- Short-wave infrared (SWIR) imaging offers advantages due to reduced light absorption and scattering.
- Rare-earth element-doped nanoprobes provide spectrally distinct emissions for multiplexed imaging.
Purpose of the Study:
- To engineer a multi-colored nanoprobe library for targeting diverse tumor biomarkers.
- To develop biocompatible SWIR-emitting nanoprobes for in vivo optical molecular imaging.
- To validate the in vivo targeting and imaging capabilities of these nanoprobes in preclinical tumor models.
Main Methods:
- Synthesized SWIR-emitting rare-earth-doped albumin nanocomposites (ReANCs) via coacervation.
- Incorporated visible light-emitting fluorophores and conjugated targeting ligands (daidzein, AMD3100, folic acid) to Ho, Er, and Tm nanoprobes.
- Validated probe specificity through in vitro uptake studies and whole-body SWIR imaging in tumor-bearing mice.
Main Results:
- Ligand-functionalized nanoprobes demonstrated significantly higher uptake in targeted cell lines and tumors compared to untargeted probes.
- Accumulation of tumor-specific nanoprobes was increased in subcutaneous models of breast and ovarian cancer.
- SWIR imaging revealed preferential accumulation in tumors overexpressing specific biomarkers in mice with bilateral tumors.
Conclusions:
- Multispectral SWIR-emitting nanoprobes can effectively detect tumors in vivo.
- These nanoprobes enable imaging of distinct biomarkers in heterogeneous tumors.
- The findings support applications in optical molecular imaging of complex tumors and studying targeted therapy responses.
