Abstract
Drug localization, release control, and penetration into solid tissues through biological tight junctions are crucial for the treatment of localized diseases with biological barriers by maximizing therapeutic efficacy of the drug and minimizing damage to normal organs. Here, we introduce a dual-phoretic wireless drug delivery system that harnesses the physical control of ion transportation: electrophoresis for controllable release and iontophoresis for directional penetration. Adjustable, pulsatile, and repeatable drug release under biological conditions is achieved using ion diodes and Zn-based electrochemical cells. Through seamless integration with iontophoretic compartments, a fourfold improvement in delivery efficiency compared to drug diffusion, reaching the core of in vivo tumor, is verified by a 3D tomographic analysis. Fully implantable and wireless operation in a simulated 2-week therapeutic scenario results in a remarkable 50% tumor reduction from the initial volume while minimizing damage to nearby normal tissue and off-target organs such as the heart, liver, spleen, and kidney.