A Light‐Activated Theranostic Nanoagent for Targeted Macrophage Ablation in Inflammatory Atherosclerosis
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The synthesis and utility of a multimodal theranostic nanoagent based upon magnetofluorescent nanoparticles for the treatment of inflammatory atherosclerosis is described. These particles are modified with near‐infrared fluorophores and light‐activated therapeutic moieties, which allow for the optical determination of agent localization and phototoxic activation at spectrally distinct wavelengths. The resulting agent is readily taken up by murine macrophages in vitro and is highly phototoxic, with an LD 50 of 430 p M . Intravenous administration results in the localization of the nanoagent within macrophage‐rich atherosclerotic lesions that can be imaged by intravital fluorescence microscopy. Irradiation of the atheroma with 650 nm light activates the therapeutic component and results in eradication of inflammatory macrophages, which may induce lesion stabilization. Importantly, these agents display limited skin photosensitivity, are highly efficacious, and provide an integrated imaging and therapeutic nanoplatform for atherosclerosis.
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In APOE-knockout mice, near-infrared light-activated dextran-coated iron oxide nanoparticles targeted to macrophages, after accumulation and laser irradiation, caused extensive macrophage cell death and apoptosis in plaques.
“McCarthy et al.84 injected a near-infrared light-activated nanoparticle based on dextran-coated iron oxide into APOE-knockout mice for targeted macrophage ablation.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [84]
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- Authors
- McCarthy, J. R., Korngold, E., Weissleder, R., & Jaffer, F. A.
- Affiliations
- Harvard University (US)
- Corresponding author
- McCarthy, Jason R.
- Jaffer, Farouc A.
- Venue
- Small
- Publisher
- Wiley
- Published
- 2010-08-18
- Volume
- 6
- Issue
- 18
- Pages
- 2041-2049
- ISSN
- 1613-6810 (ISSN-L)
- 1613-6829
- PMC
- PMC3018665
- OpenAlex
- W2140608909
- Cited by
- 151
- References
- 37
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 14 · 2023: 9 · 2022: 7 · 2021: 9 · 2020: 7 · 2019: 11 · 2018: 9 · 2017: 7 · 2016: 8 · 2015: 15 · 2014: 15 · 2013: 10 · 2012: 10
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Small (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (U01HL080731, R21HL093607)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- macrophage depletion, near-infrared fluorescence imaging, atherosclerotic plaque stabilization, intravital fluorescence microscopy, photodynamic therapy, skin photosensitivity
- MeSH terms
- Animals, Apolipoproteins E, Cell Separation, Cells, Cultured, Female, Inflammation, Light, Macrophages, Male, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Phototherapy, Drug Delivery Systems, Nanostructures, Atherosclerosis, Mice
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