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.
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The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analyzed datasets generated during the study are too large to be publicly shared but are available for research purposes from the corresponding authors on reasonable request. Source data are provided with this paper.
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This study was supported in part by the following grants from the National Institutes of Health: K99/R00HL121152 (to H.H.C.), R01HL112831 and R01HL141563 (to D.E.S.), R01HL122547 and R01HL102368-06A1 (to S.D.), R01HL131635 (to C.M.) and R01HL131831 (to R.M.B.). Electron microscopy was performed in the Microscopy Core of the Center for Systems Biology/Program in Membrane Biology, which is partially supported by an Inflammatory Bowel Disease Grant (DK043351) and a Boston Area Diabetes and Endocrinology Research Center (BADERC) award (DK057521). The funders had no role in the design of the study, in data collection and analysis, in the decision to publish the manuscript or in its preparation.
The authors declare no competing interests.
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Chen, H.H., Khatun, Z., Wei, L. et al. A nanoparticle probe for the imaging of autophagic flux in live mice via magnetic resonance and near-infrared fluorescence. Nat. Biomed. Eng 6, 1045–1056 (2022). https://doi.org/10.1038/s41551-022-00904-3
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