Li Zhaojun, Huang Hui, Huang Lili, Du Lianfang, Sun Ying, Duan Yourong
Department of Ultrasound, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China.
Int J Mol Sci. 2017 Apr 13;18(4):815. doi: 10.3390/ijms18040815.
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.
一般来说，动脉粥样硬化被认为是一种慢性炎症形式。地塞米松在动脉粥样硬化中具有抗炎作用，但由于其不良的药代动力学特征和副作用，不考虑长期给药。药物可溶解、封装、包埋或化学附着于颗粒表面的纳米颗粒具有包载地塞米松的能力，并可用作控释或靶向给药系统。长循环聚合物纳米颗粒是一种在动脉粥样硬化部位实现包封药物控释和靶向释放的辅助方法。聚合物纳米颗粒与超声（US）相结合，因其应用时间长、成本低、操作简单和安全性高，在癌症治疗中得到广泛应用。然而，关于聚合物纳米颗粒联合超声治疗动脉粥样硬化的研究很少。在本研究中，采用乳化蒸发法，以cRGD修饰的聚乳酸-乙醇酸-聚乙二醇（PLGA-PEG-cRGD）聚合物材料为载体，制备了靶向载醋酸地塞米松（DA）的聚（乳酸-乙醇酸）-聚乙二醇-cRGD（PLGA-PEG-cRGD）纳米颗粒（DA-PLGA-PEG-cRGD NPs）。DA-PLGA-PEG-cRGD NPs的平均粒径为221.6±0.9nm。纳米颗粒形态呈球形且分散均匀。此外，DA释放曲线表明超声可促进药物从纳米载体中释放并加速释放速率。在体外，异硫氰酸荧光素（FITC）@DA-PLGA-PEG-cRGD NPs联合超声进入受损人脐静脉内皮细胞（HUVECs）的细胞摄取过程表明，超声促进了FITC@DA-PLGA-PEG-cRGD NPs在细胞内的快速摄取。DA-PLGA-PEG-cRGD NPs联合超声的细胞活力达到91.9%±0.2%，这表明DA-PLGA-PEG-cRGD NPs联合超声对受损的HUVECs具有积极的治疗作用。总体而言，DA-PLGA-PEG-cRGD NPs联合超声可能提供一种有前景的给药系统，以在细胞水平上增强这些化疗药物的治疗效果。
