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

Huoyan Hong; Xiaoyun Wang; Xinran Song; Gomaa El Fawal; Kaili Wang; Di Jiang; Yifei Pei; Zhe Wang; Hongsheng Wang

doi:10.12336/biomatertransl.2021.02.005

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

Biomater Transl. 2021 Jun 28;2(2):151-164. doi: 10.12336/biomatertransl.2021.02.005. eCollection 2021.

Authors

Huoyan Hong¹, Xiaoyun Wang², Xinran Song¹, Gomaa El Fawal^{1

3}, Kaili Wang¹, Di Jiang¹, Yifei Pei¹, Zhe Wang¹, Hongsheng Wang¹

Affiliations

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.

PMID: 35836967
PMCID: PMC9255785
DOI: 10.12336/biomatertransl.2021.02.005

Abstract

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 (p^IL-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 p^IL-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-p^IL-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.

Keywords: IL-12; aPD-1; dendritic cells; ethosome; transcutaneous immunization.

Grants and funding

This work was supported by the Science & Technology Commission of Shanghai Municipality of China, Nos. 18490740400, 20DZ2254900; and the National Key Research & Development Program of China, No. 2018YFC1706200.