Delivery of mRNA vaccines and anti-PDL1 siRNA through non-invasive transcutaneous route effectively inhibits tumor growth

This study aimed to deliver mRNA vaccines and immune checkpoint blockers (ICB) with a transcutaneous immunization (TCI) system based on ethosomes (ETH), exploring the feasibility and effectiveness of their use in tumor treatment. Our data showed that the mannosylated-chitosan-modified ETH (ETHMC) loaded with mRNA can efficiently transfect dendritic cells (DCs) and induce them maturation. The transdermal patches loaded with mRNA vaccines (termed TCIP) or siRNA against PDL1 (termed TDSP) were prepared by electrospraying microspheres containing mRNA- or siRNA-loaded ETHMC onto the surface of silk fibroin matrices (SFM). The patches showed a good transdermal performance and can effectively deliver nucleic acid molecules into the deep layers of skin. In vivo experiments showed that TCIP loaded with mRNA vaccines can effectively trigger cellular and humoral immune responses. Using mouse melanoma as a model, the combined treatment with TCIP and TDSP showed good antitumor effect, significantly inhibiting tumor growth by improving the infiltration of CD4+ and CD8+ T cells as well as the apoptosis rates in tumor tissues. Our work provides a new strategy for tumor treatment by integrating the non-invasive and convenient of TCI and the flexibility of RNA therapy.