A battery-free, chipless, soft nanofluidic intracellular delivery patch for internal organs

Abstract Internal organ targeted delivery to enable gene editing and induced apoptosis among others, holds tremendous promise in treating numerous challenging diseases. The current and dominant method is circulation-based delivery; yet it has critical limitations on the efficiency, safety, and/or controllability. Here, we report a battery-free, chipless, soft nanofluidic intracellular delivery (NanoFLUID) patch that is capable of enhanced, customized delivery in targeted internal organs. The chipless architecture and the flexible nature of thin functional layers ensure seamless integration with internal organs. The unique nanopore-microchannel-microelectrode structure renders unprecedented features of safe, efficient, precise electro-perforation of cell membrane and of accelerated intracellular payload transport by 104 – 105 times compared with conventional diffusion methods, while operating under relatively low amplitude pulses (20V or less). It was demonstrated that the NanoFLUID patch could achieve customized delivery into mammary gland of adult mice for gene editing to construct both primary and metastatic breast tumor models. The patch showed high efficiency for transfecting a gene pool of more than 40 genes in cells within a targeted organ. It was further demonstrated that the NanoFLUID patch based three-time iterative delivery of a cancer inhibitor (PARPi) could achieved similar breast tumor inhibition as that from daily oral administration for three weeks.