Magnetic Force-driven in Situ Selective Intracellular Delivery

Intracellular delivery of functional materials holds great promise in biologic research and therapeutic applications but poses challenges to existing techniques, including the reliance on exogenous vectors and lack of selectivity. To address these problems, we propose a vector-free approach that utilizes millimeter-sized iron rods or spheres driven by magnetic forces to selectively deform targeted cells, which in turn generates transient disruption in cell membranes and enables the delivery of foreign materials into cytosols. A range of functional materials with the size from a few nanometers to hundreds of nanometers have been successfully delivered into various types of mammalian cells in situ with high efficiency and viability and minimal undesired effects. Mechanistically, material delivery is mediated by force-induced transient membrane disruption and restoration, which depend on actin cytoskeleton and calcium signaling. When used for siRNA delivery, CXCR4 is effectively silenced and cell migration and proliferation are significantly inhibited. Remarkably, cell patterns with various complexities are generated, demonstrating the unique ability of our approach in selectively delivering materials into targeted cells in situ. In summary, we have developed a magnetic force-driven intracellular delivery method with in situ selectivity, which may have tremendous applications in biology and medicine.