Biomaterials Translational ›› 2021, Vol. 2 ›› Issue (2): 151-164.doi: 10.12336/biomatertransl.2021.02.005

• RESEARCH ARTICLE • Previous Articles     Next Articles

Transdermal delivery of interleukin-12 gene targeting dendritic cells enhances the anti-tumour effect of programmed cell death protein 1 monoclonal antibody

Huoyan Hong1,#, Xiaoyun Wang2,#, Xinran Song1, Gomaa El Fawal1,3, Kaili Wang1, Di Jiang1, Yifei Pei1, Zhe Wang1, Hongsheng Wang1,*()   

  1. 1 Shanghai Engineering Research Centre of Nano-Biomaterials and Regenerative Medicine, Key Laboratory of Science & Technology of Eco-Textile (Ministry of Education), College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China
    2 Department of Obstetrics & Gynaecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
    3 Department of Polymer Materials Research, Advanced Technology and New Materials Research Institute, Scientific Research and Technological Applications City (SRTA-City), New Borg El-Arab City, Alexandria, Egypt
  • Received:2021-04-17 Revised:2021-06-04 Accepted:2021-06-07 Online:2021-06-28 Published:2021-06-28
  • Contact: Hongsheng Wang E-mail:whs@dhu.edu.cn
  • About author:#Author equally.


Recent studies have suggested that the anti-tumour effect of the programmed cell death protein 1 monoclonal antibody (aPD-1) depends on the expression of interleukin-12 (IL-12) by dendritic cells (DCs). Since DCs are abundant in skin tissues, transdermal delivery of IL-12 targeting DCs may significantly improve the anti-tumour effect of aPD-1. In this study, a novel mannosylated chitosan (MC)-modified ethosome (Eth-MC) was obtained through electrostatic adsorption. The Eth-MC loaded with plasmid containing the IL-12 gene (pIL-12@Eth-MC) stimulated DCs to express mature-related molecular markers such as CD86, CD80, and major histocompatibility complex-II in a targeted manner. The pIL-12@Eth-MC was then mixed with polyvinyl pyrrolidone solution to make microspheres using the electrospray technique, and sprayed onto the surface of electrospun silk fibroin-polyvinyl alcohol nanofibres to obtain a PVP-pIL-12@Eth-MC/silk fibroin-polyvinyl alcohol composite nanofibrous patch (termed a transcutaneous immunization (TCI) patch). The TCI patch showed a good performance on transdermal drug release. Animal experiments on melanoma-bearing mice showed that topical application of the TCI patches promoted the expression of IL-12 and inhibited the growth of tumour. Furthermore, combined application of the TCI patch and aPD-1 showed a stronger anti-tumour effect than aPD-1 monotherapy. The combination therapy significantly promoted the expression of IL-12, interferon-γ and tumour necrosis factor-α, the infiltration of CD4+ and CD8+ T cells into tumour tissues, and thus promoted the apoptosis of tumour cells. The present study provides a convenient and non-invasive strategy for improving the efficacy of immune checkpoint inhibitor therapy. This study was approved by the Institutional Animal Care and Use Committee at Donghua University (approval No. DHUEC-NSFC-2020-11) on March 31, 2020.

Key words: aPD-1, dendritic cells, ethosome, IL-12, transcutaneous immunization