Fuior Elena Valeria, Mocanu Cristina Ana, Deleanu Mariana, Voicu Geanina, Anghelache Maria, Rebleanu Daniela, Simionescu Maya, Calin Manuela
"Medical and Pharmaceutical Bionanotechnologies" Laboratory, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania.
"Liquid and Gas Chromatography" Laboratory, Department of Lipidomics, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania.
Pharmaceutics. 2020 Nov 9;12(11):1066. doi: 10.3390/pharmaceutics12111066.
Naringenin, an anti-inflammatory citrus flavonoid, is restrained from large-scale use by its reduced water solubility and bioavailability. To overcome these limitations, naringenin was loaded into lipid nanoemulsions directed towards vascular cell adhesion molecule (VCAM)-1, exposed by activated endothelium, and delivered intravenously in a murine model of lipopolysaccharide (LPS)-induced inflammation. To follow the in vivo bio-distribution, naringenin-loaded nanoemulsions were labeled with near-infrared probe Indocyanine Green (ICG). Based on ICG fluorescence, a VCAM-1-dependent retention of nanoemulsions was detected in the heart and aorta, while ultra-high-performance liquid chromatography (UHPLC) measurements showed a target-selective accumulation of naringenin in the heart and lungs. Correlated, fluorescence and UHPLC data indicated a mixed behavior of the VCAM-1 directed nanoparticles, which were driven not only by the targeting moiety but also by passive retention. The treatment with naringenin-loaded nanoemulsions reduced the mRNA levels of some inflammatory mediators in organs harvested from mice with acute inflammation, indicative of their anti-inflammatory potential. The data support a novel theranostic nanoplatform for inflammation, the naringenin/ICG-loaded nanoparticles that either by passive accumulation or effective targeting of the activated endothelium can be employed for imaging inflamed vascular areas and efficient delivery of the encapsulated therapeutic agent.
柚皮素是一种具有抗炎作用的柑橘类黄酮，但其水溶性和生物利用度较低，限制了其大规模应用。为克服这些局限性，将柚皮素载入靶向血管细胞黏附分子（VCAM）-1的脂质纳米乳剂中，VCAM-1由活化的内皮细胞暴露，然后在脂多糖（LPS）诱导的炎症小鼠模型中静脉给药。为追踪体内生物分布，用近红外探针吲哚菁绿（ICG）标记载有柚皮素的纳米乳剂。基于ICG荧光，在心脏和主动脉中检测到纳米乳剂依赖于VCAM-1的滞留，而超高效液相色谱（UHPLC）测量显示柚皮素在心脏和肺中具有靶向选择性积累。相关的荧光和UHPLC数据表明，靶向VCAM-1的纳米颗粒具有混合行为，这不仅由靶向部分驱动，还由被动滞留驱动。用载有柚皮素的纳米乳剂治疗可降低急性炎症小鼠器官中一些炎症介质的mRNA水平，表明其具有抗炎潜力。这些数据支持了一种用于炎症的新型诊疗纳米平台，即载有柚皮素/ICG的纳米颗粒，其可通过被动积累或有效靶向活化的内皮细胞，用于对炎症血管区域进行成像以及高效递送封装的治疗剂。
