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

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

机构地区：[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

出　　处：《Biomaterials Translational》2021年第2期151-164,共14页生物材料转化电子杂志（英文）

基　　金：supported by the Science&Technology Commission of Shanghai Municipality of China,Nos.18490740400,20DZ2254900;the National Key Research&Development Program of China,No.2018YFC1706200.

摘　　要：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-γand 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.

关 键 词：aPD-1 dendritic cells ethosome IL-12 transcutaneous immunization 

分 类 号：R73[医药卫生—肿瘤]