近红外荧光纳米探针对预防心肌缺血再灌注损伤药物的抗氧化效力的实时可视化,ACS Sensors

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近红外荧光纳米探针对预防心肌缺血再灌注损伤药物的抗氧化效力的实时可视化
ACS Sensors ( IF 8.2 ) Pub Date : 2022-11-28 , DOI: 10.1021/acssensors.2c01857
Aiping Shi ₁ , Yuling Zeng ₁ , Dongxu Xin ₁ , Yunyun Zhou ₁ , Lingzhi Zhao ₁ , Juanjuan Peng ₁

Affiliation

活性氧（ROS）的爆发是心肌缺血再灌注损伤的罪魁祸首。作为直接的 ROS 清除剂，抗氧化剂是临床上记录的用于预防再灌注损伤的药物。然而，一些药物尽管具有良好的体外效果，但其治疗效果却令人失望。因此，在临床试验之前，有必要进行体内评估以筛选抗氧化剂。然而，组织学研究等传统方法需要对生物样本进行侵入性和复杂的预处理，这可能无法反映寿命很短的不稳定 ROS 的实际水平。过氧亚硝酸盐 (ONOO ^– ) 是再灌注过程中产生的一种特征性内源性 ROS。^在这里，我们修改了 ONOO——-在心肌靶向二氧化硅交联胶束上的响应性近红外荧光探针，以制备用于冠状动脉再灌注期间实时监测 ONOO 的纳米探针^。ROS 稳定的花青染料被共同标记为内部参考以实现比例传感。纳米探针可以被动靶向梗死心肌并监测ONOO的产生^——在实时再灌注期间。抗氧化剂卡维地洛、阿托伐他汀和白藜芦醇被用作模型药物，以证明纳米探针在原位评估抗氧化效力的能力。这些药物要么由纳米探针加载和递送，以比较它们在相似浓度下的体内功效，要么作为游离药物腹膜内给药，以考虑它们的药代动力学。成像结果表明，药代动力学可能是影响抗氧化剂功效的决定性因素。

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Real-Time Visualization of the Antioxidative Potency of Drugs for the Prevention of Myocardium Ischemia-Reperfusion Injury by a NIR Fluorescent Nanoprobe

The burst of the reactive oxygen species (ROS) is the culprit of myocardial ischemia-reperfusion injury. As direct ROS scavengers, antioxidants are clinically documented drugs for the prevention of reperfusion injury. However, some drugs give disappointing therapeutic performance despite their good in vitro effects. Therefore, in vivo assessments are necessary to screen the antioxidants before clinical trials. However, traditional methods such as histological study require invasive and complicated preprocessing of the biological samples, which may fail to reflect the actual level of the unstable ROS with a very short lifetime. Peroxynitrite (ONOO^–) is a characteristic endogenous ROS produced during reperfusion. Here, we modified the ONOO^–-responsive near-infrared fluorescent probe on a myocardium-targeting silica cross-linked micelle to prepare a nanoprobe for the real-time monitoring of ONOO^– during coronary reperfusion. A ROS-stable cyanine dye was co-labeled as an internal reference to achieve ratiometric sensing. The nanoprobe can passively target the infarcted myocardium and monitor the generation of ONOO^– during reperfusion in real-time. The antioxidants, carvedilol, atorvastatin, and resveratrol, were used as model drugs to demonstrate the capability of the nanoprobe to evaluate the antioxidative potency in situ. The drugs were either loaded and delivered by the nanoprobe to compare their in vivo efficacy under similar concentrations or administered intraperitoneally as a free drug to take their pharmacokinetics into account. The imaging results revealed that pharmacokinetics might be the determinant factor that influences the efficacy of the antioxidants.

更新日期：2022-11-28

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