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Nanosphere-mediated co-delivery of VEGF-A and PDGF-B genes for accelerating diabetic foot ulcers healing in rats

Gene Therapy volume 25, pages 425–438 (2018)Cite this article

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Abstract

Diabetic ischemic ulcer is an intractable diabetic complication. Angiogenesis is a critical factor for wound healing in patients with diabetic foot wounds. Sustained gene delivery could be notably necessary in modulating gene expression in chronic ulcer healing and might be a promising approach for diabetic foot ulcers. In the present study, Sprague–Dawley rats were used to establish diabetic foot ulcer models by streptozotocin and skin biopsy punch. The plasmids expressing VEGF-A and PDGF-B were prepared and then incorporated with polylactic-co-glycolic acid (PLGA) nanospheres to upregulate genes expression. The aim of this study was to explore whether the engineered VEGF-A and PDGF-B based plasmid-loaded nanospheres could be upregulated in streptozotocin-induced diabetic rats and improve the wound healing. The cultured fibroblasts could be effectively transfected by means of nanosphere/plasmid in vitro. In vivo, the expression of VEGF-A and PDGF-B was significantly upregulated at full-thickness foot dorsal skin wounds and the area of ulceration was progressively and significantly reduced following treatment with nanosphere/plasmid. These results indicated that combined gene transfer of VEGF-A and PDGF-B could improve reparative processes in the wounded skin of diabetic rats and nanosphere may be a potential non-viral vector for gene therapy of the diabetic foot ulcer.

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Funding

This work was supported by the Natural Science Foundation of China [grant number 81071242], the International Exchange Program for Graduate Students, Tongji University [grant number 2016XJKC-014]

Author contributions

RS, WL, SH, and ML contributed to the conception, design, and experiments of the study; manuscript preparation and were responsible for collecting data. SH, CC, YJ, and YY carried out the experiment and analyzed data; RS, WL, HZ, and ML wrote and edited the main manuscript text, and all of the authors discussed the results and proofread on the submitted versions.

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Author notes

  1. These authors contributed equally: Rongfeng Shi, Weishuai Lian, Shilong Han.

Authors and Affiliations

  1. Department of Interventional Radiology, Affiliated Hospital of Nantong University, 226101, Nantong, Jiangsu, China

    Rongfeng Shi & Hui Zhao

  2. Department of Interventional & Vascular Surgery, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, 200072, Shanghai, China

    Weishuai Lian, Shilong Han, Chuanwu Cao, Yifeng Yuan & Maoquan Li

  3. Institute of Medical Intervention Engineering, Tongji University, 200072, Shanghai, China

    Weishuai Lian, Shilong Han, Chuanwu Cao & Maoquan Li

  4. Shanghai Liver Diseases Research Center, The Nanjing Military Command, 200235, Shanghai, China

    Yinpeng Jin

Authors
  1. Rongfeng Shi
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  2. Weishuai Lian
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  7. Hui Zhao
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  8. Maoquan Li
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Correspondence to Hui Zhao or Maoquan Li.

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Shi, R., Lian, W., Han, S. et al. Nanosphere-mediated co-delivery of VEGF-A and PDGF-B genes for accelerating diabetic foot ulcers healing in rats. Gene Ther 25, 425–438 (2018). https://doi.org/10.1038/s41434-018-0027-6

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  • DOI: https://doi.org/10.1038/s41434-018-0027-6

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