A nanoparticle probe for the imaging of autophagic flux in live mice via magnetic resonance and near-infrared fluorescence

• Published in: Nature biomedical engineering Vol. 6; no. 9; pp. 1045 - 1056
• Main Authors: Chen, Howard H., Khatun, Zehedina, Wei, Lan, Mekkaoui, Choukri, Patel, Dakshesh, Kim, Sally Ji Who, Boukhalfa, Asma, Enoma, Efosa, Meng, Lin, Chen, Yinching I., Kaikkonen, Leena, Li, Guoping, Capen, Diane E., Sahu, Parul, Kumar, Anand T. N., Blanton, Robert M., Yuan, Hushan, Das, Saumya, Josephson, Lee, Sosnovik, David E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2022; Nature Publishing Group
• Subjects: 14; 14/10; 59; 631/1647/245/2160; 631/1647/245/2225; 631/61/350; 692/699/75; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Antibiotics; Arginine - chemistry; Autophagy; Autophagy - drug effects; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Carbocyanines - chemistry; Cathepsins; Cathepsins - chemistry; Chemotherapy; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Fluorescence; Fluorescent Dyes - chemistry; I.R. radiation; Infrared imaging; Intravenous administration; Iron oxides; Ischemia; Lysosomes; Macrolides - administration & dosage; Macrolides - pharmacology; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Medical imaging; Mice; Nanoparticles; Nanoparticles - chemistry; Peptides; Phagosomes; Reperfusion; Spectroscopy, Near-Infrared - methods; Starvation
• ISSN: 2157-846X; 2157-846X
• DOI: 10.1038/s41551-022-00904-3

Autophagy—the lysosomal degradation of cytoplasmic components via their sequestration into double-membraned autophagosomes—has not been detected non-invasively. Here we show that the flux of autophagosomes can be measured via magnetic resonance imaging or serial near-infrared fluorescence imaging of intravenously injected iron oxide nanoparticles decorated with cathepsin-cleavable arginine-rich peptides functionalized with the near-infrared fluorochrome Cy5.5 (the peptides facilitate the uptake of the nanoparticles by early autophagosomes, and are then cleaved by cathepsins in lysosomes). In the heart tissue of live mice, the nanoparticles enabled quantitative measurements of changes in autophagic flux, upregulated genetically, by ischaemia–reperfusion injury or via starvation, or inhibited via the administration of a chemotherapeutic or the antibiotic bafilomycin. In mice receiving doxorubicin, pre-starvation improved cardiac function and overall survival, suggesting that bursts of increased autophagic flux may have cardioprotective effects during chemotherapy. Autophagy-detecting nanoparticle probes may facilitate the further understanding of the roles of autophagy in disease. The flux of autophagosomes in the heart tissue of mice can be imaged via the intravenous injection of iron oxide nanoparticles decorated with fluorescent peptides cleavable by lysosomal cathepsins.