Rolling microneedle electrode array (RoMEA) empowered nucleic acid delivery and cancer immunotherapy

Topical administration of siRNA, a clinically approved promising therapeutic modality, represents a much more transformative approach for drug development, compared to intravenous injection. To implement an efficient and extensive siRNA therapy in vivo, we engineered a rolling microneedle electrode array (RoMEA), which utilizes parallel circular blades with microneedle arrays on edge as electrodes. RoMEA integrates close-spaced microneedle electrodes and rolling structure to allow low-damage and large-area siRNA transfection. Upon applying RoMEA, regular micropores were established, efficient siRNA delivery and gene silence were achieved. In addition, employments of siRNA targeting programmed death-ligand 1 (PD-L1) alone, or combined with anti-programmed death-1 (PD-1) antibody or immunoadjuvant of CpG2395, in two tumor xenograft murine models demonstrated that proposed strategies restored efficient T cell immune response, conferring significant tumor growth inhibition with excellent safety profiles. RoMEA constitutes an unprecedented and ingenious clinic solution to large-area local delivery of nucleic acid for cancer immunotherapy.