Bilayered Nanoparticles with Sequential Release of VEGF Gene and Paclitaxel for Restenosis Inhibition in Atherosclerosis

Xiaowei Zhu, Hongzhi Xie, Xiaoyu Liang, Xuanling Li, Jianwei Duan, Yongxia Chen, Ziying Yang, Chao Liu, Cuiwei Wang, Hailing Zhang, Quan Fang, Hongfan Sun, Chen Li, Yongjun Li, Chun Wang, Cunxian Song, Yong Zeng, Jing Yang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Complete reendothelialization followed by inhibition of smooth muscle cell (SMC) proliferation is considered as an effective therapeutic option to prevent restenosis. We have designed poly(lactide-co-glycolide)-loaded bilayered nanoparticles (NPs) with the ability to sequentially release vascular endothelial growth factor (VEGF)-encoding plasmids from the outer layer and paclitaxel (PTX) from the core to promote endothelial regeneration as well as prevent restenosis. Comparing with conventional NPs, which release VEGF plasmid and PTX simultaneously, we expect that the bilayered NPs could release the VEGF plasmid more rapidly, followed by a delayed release of PTX, resulting in an efficient VEGF gene transfection, which ideally could promote reendothelialization and inhibit excessive SMC growth. Indeed, in the present study, we have observed efficient gene transfection using a model plasmid as well as cell growth attenuation in vitro using Chinese hamster ovary cells. Therapeutic efficacy of the bilayered NPs on restenosis was further evaluated in vivo using a rabbit model of atherosclerosis. The bilayered NPs were administered locally via balloon angioplasty to the injured aortic wall through perfusion. Twenty-eight days after the NP administration, rabbits treated with the bilayered NPs exhibited rapid reendothelialization and inhibition of restenosis, as demonstrated by histological analysis. Increased level of VEGF and decreased level of C-reactive protein, a biological marker that is closely related to atherosclerosis, were also observed from animals treated with the bilayered NPs, implicating ameliorated atherosclerosis. Our results suggest that the VEGF plasmid-/PTX-loaded bilayered NPs exert a beneficial impact on atherosclerotic restenosis by sequentially releasing VEGF and PTX in vivo.

Original languageEnglish (US)
Pages (from-to)27522-27532
Number of pages11
JournalACS Applied Materials and Interfaces
Volume9
Issue number33
DOIs
StatePublished - Aug 23 2017

Keywords

  • atherosclerosis
  • balloon reperfusion
  • nanoparticles
  • reendothelialization
  • restenosis

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    Zhu, X., Xie, H., Liang, X., Li, X., Duan, J., Chen, Y., Yang, Z., Liu, C., Wang, C., Zhang, H., Fang, Q., Sun, H., Li, C., Li, Y., Wang, C., Song, C., Zeng, Y., & Yang, J. (2017). Bilayered Nanoparticles with Sequential Release of VEGF Gene and Paclitaxel for Restenosis Inhibition in Atherosclerosis. ACS Applied Materials and Interfaces, 9(33), 27522-27532. https://doi.org/10.1021/acsami.7b08312