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.

自噬——细胞质成分通过被隔离到双膜自噬体中的溶酶体降解——尚未被非侵入性地检测到。在这里，我们表明，可以通过静脉注射的氧化铁纳米颗粒的磁共振成像或连续近红外荧光成像来测量自噬体的通量，这些氧化铁纳米颗粒装饰有组织蛋白酶可裂解的富含精氨酸的肽，该肽用近红外荧光染料 Cy5.5 功能化（肽）促进早期自噬体摄取纳米颗粒，然后被溶酶体中的组织蛋白酶切割）。在活体小鼠的心脏组织中，纳米颗粒能够定量测量自噬通量的变化，这些变化可以通过缺血再灌注损伤或饥饿进行基因上调，或者通过化疗或抗生素巴弗洛霉素的施用进行抑制。在接受阿霉素的小鼠中，饥饿前改善了心脏功能和总体生存率，这表明自噬通量的爆发可能在化疗期间具有心脏保护作用。自噬检测纳米颗粒探针可能有助于进一步了解自噬在疾病中的作用。