An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo.
An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo.
复制标题
DOI：
10.1126/scitranslmed.aar2680
复制
发表时间：
2018-10-03
影响因子：
17.1
通讯作者：
Heller DA
中科院分区：
文献类型：
--
作者：
Galassi TV;Jena PV;Shah J;Ao G;Molitor E;Bram Y;Frankel A;Park J;Jessurun J;Ory DS;Haimovitz-Friedman A;Roxbury D;Mittal J;Zheng M;Schwartz RE;Heller DA
内溶酶体腔内脂质的异常积聚发生在许多病症中，包括溶酶体贮积症、动脉粥样硬化、非酒精性脂肪肝病（NAFLD）和药物诱导的磷脂质病。目前的方法不能在体内监测内溶酶体脂质含量，阻碍了临床前药物开发和对内溶酶体脂质蓄积与疾病进展相关机制的研究。我们开发了一种基于单壁碳纳米管的光学报告器，其通过其固有近红外发射的带隙调制非侵入性地测量内溶酶体脂质积累。报告者在体内尼曼-皮克病、动脉粥样硬化和NAFLD模型中检测到脂质蓄积。通过将报告者应用于NAFLD的研究，我们发现由高脂肪饮食引起的肝巨噬细胞中脂质含量升高在恢复正常饮食后持续很长时间。报告者在几分钟到几周的时间尺度内动态监测了体内内溶酶体脂质蓄积，表明其有可能加速临床前研究和药物开发过程。一种nanorporter非侵入性检测内溶酶体脂质，揭示了饮食的短期变化对肝巨噬细胞具有持久的影响。
The abnormal accumulation of lipids within the endolysosomal lumen occurs in many conditions, including lysosomal storage disorders, atherosclerosis, non-alcoholic fatty liver disease (NAFLD), and drug induced phospholipidosis. Current methods cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug development and research into the mechanisms linking endolysosomal lipid accumulation to disease progression. We developed a single-walled carbon nanotube-based optical reporter that non-invasively measures endolysosomal lipid accumulation via bandgap modulation of its intrinsic near-infrared emission. The reporter detected lipid accumulation in Niemann-Pick disease, atherosclerosis, and NAFLD models in vivo. By applying the reporter to the study of NAFLD, we found that elevated lipid quantities in hepatic macrophages caused by a high fat diet persist long after reverting to a normal diet. The reporter dynamically monitored endolysosomal lipid accumulation in vivo over time scales ranging from minutes to weeks, indicating its potential to accelerate preclinical research and drug development processes. A nanoreporter non-invasively detects endolysosomal lipids, revealing that short-term changes in diet have enduring effects on hepatic macrophages.