A light-activated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis.
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 pM. 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.
McCarthy
Jason R
JR
Harvard Medical School, Boston, MA 02114, USA. jason_mccarthy@hms.harvard.edu
Korngold
Ethan
E
Weissleder
Ralph
R
Jaffer
Farouc A
FA
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications / Q000473:pathology / Q000628:therapy*; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D007249:Inflammation / Q000150:complications / Q000473:pathology / Q000628:therapy*; D008027:Light; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D049329:Nanostructures / Q000008:administration & dosage / Q000528:radiation effects / Q000627:therapeutic use*; D010789:Phototherapy / Q000379:methods*
D001057:Apolipoproteins E