Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.
Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.
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DA-PLGA-PEG-cRGD纳米颗粒联合超声预防氧化低密度脂蛋白诱导的内皮细胞损伤
DOI：
10.3390/ijms18040815
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发表时间：
2017-04-13
影响因子：
5.6
通讯作者：
Duan Y
中科院分区：
文献类型：
--
作者：
Li Z;Huang H;Huang L;Du L;Sun Y;Duan Y
一般来说，动脉粥样硬化被认为是一种慢性炎症。地塞米松在动脉粥样硬化中具有抗炎作用，但由于药代动力学特征差和不良副作用，不考虑长期给药。其中药物可以溶解、包封、截留或化学附着到颗粒表面的纳米颗粒具有掺入地塞米松并用作受控或靶向药物递送系统的能力。长循环聚合物纳米颗粒是在动脉粥样硬化部位控制和靶向释放包裹药物的辅助方法。聚合物纳米颗粒结合超声（US）由于其时间应用、低成本、简单和安全而广泛应用于癌症治疗。然而，很少有研究使用聚合物纳米颗粒结合超声治疗动脉粥样硬化。本研究以制备的cRGD修饰的聚乳酸-聚乙二醇（PLGA-PEG-cRGD）聚合物材料为载体，采用乳化蒸发法制备了醋酸地塞米松（DA）靶向聚乳酸-聚乙二醇-cRGD（PLGA-PEG-cRGD）纳米粒（DA-PLGA-PEG-cRGD NPs）。DA-PLGA-PEG-cR ⑶ NP的平均粒径为221.6 ± 0.9 nm。纳米粒子的形貌为球形，分散均匀。此外，DA的释放曲线表明，超声可以促进药物从纳米载体中释放，加快释放速率。在体外，异硫氰酸荧光素（FITC）@DA-PLGA-PEG-cRGD NPs与US组合进入受损的人脐静脉内皮细胞（HUVECs）的细胞摄取过程表明，US促进FITC@ DA-PLGA-PEG-cRGD NPs的快速细胞内摄取。DA-PLGA-PEG-cRGD NPs联合US的细胞存活率达到91.9% ± 0.2%，表明DA-PLGA-PEG-cRGD NPs联合US对损伤的HUVECs具有积极的治疗作用。总的来说，DA-PLGA-PEG-cRGD NP与US的组合可以提供有前景的药物递送系统，以在细胞水平上增强这些化疗剂的治疗效果。
In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG-cRGD NPs in combination with US may provide a promising drug delivery system to enhance the therapeutic effects of these chemotherapeutics at the cellular level.