再狭窄
纳米载体
纳米凝胶
药物输送
材料科学
细胞毒性
癌症研究
医学
传统PCI
纳米技术
生物医学工程
药理学
化学
体外
内科学
支架
生物化学
心肌梗塞
作者
Qian Yang,Jinrong Peng,Chan Chen,Yao Xiao,Liwei Tan,Xiulan Xie,Xianglan Xu,Zhiyong Qian
标识
DOI:10.1166/jbn.2018.2588
摘要
Coronary arterial disease (CAD) remains the leading cause of death globally. Although percutaneous coronary interventions (PCI) are most of the important clinical procedure for CAD treating, unfortunately, vascular restenosis is proved as the major drawback of PCI. Because of the complex nature of the restenotic process, the efficacy of drug administration is emphasized. Targeting drug delivery systems become a promising experimental approach for restenosis therapy. Hence, we design and fabricate a thermo/pH-responsive nanogel system with the magnetic inner core as the multifunctional nanocarrier for drug delivery and MRI/fluorescence imaging. To this end, NIPAm-based Fe3O4 core-shell structure nanogel is synthesized as the responsive nanosystem for rapamycin (RAPA) delivery, and the surface conjugation with anti-collagen IV peptide makes the nanosystem an ideal candidate for targeting delivery of RAPA. Based on its stimuliresponsive properties, the nanosystem shows desirable intracellular release behavior of RAPA and significantly reduces the adverse effect of RAPA. The in vitro cytotoxicity evaluations present the biosafety profiles and antiproliferation performance of the drug-loaded nanogels. Meanwhile, the magnetic Fe3O4 inner core shows enhanced T2 weight sensitivity, providing a high potential for imaging-guiding therapy. In the balloon angioplasty model, targeting nanogels are demonstrated accumulation at the injured site of artery. Compared with the non-targeting nanogels, treatment with peptide conjugated nanogels attenuates neointimal hyperplasia more effectively. The biochemical assays further reveal that the enhanced restenosis prevention effect is contributed to the selective release of RAPA at the injured sites of artery, which notably potentiate the nanosystem as a systemically targeting delivered treatment.
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