Multimicrochannel Microneedle Microporation Platform for Enhanced Intracellular Drug Delivery

Abstract Common delivery routes for chemotherapeutics are based on circulation, which faces clinical limitations to local delivery efficiency, and the conflict between the dose for anticancer effect and the systemic toxicity. The recent advances in localized delivery strategies aim to improve drug accumulation at the target site or directly transport into cells. However, most are not equipped to provide additional momentum in the process of cargo release, propagation, and intracellular movement, which limit their locomotion that relies on passive diffusion. In this work, a multimicrochannel microneedle microporation (4M) platform that achieves high efficiency, safety, and uniformity for in vivo intracellular delivery is proposed. By high precision 3D printing, internal microchannels are implemented through the microneedle, which offer a concentrated, safe electric field that not only accelerates the movement of cargo into deep tissue under electrophoresis, but also triggers cell electroporation, achieving enhanced transport across cell membrane. The platform proves efficient for the delivery of chemotherapeutics in solid tumors in vitro and in vivo, with significantly enhanced anticancer effect and reduced systemic toxicity. The platform serves as a general‐purpose delivery tool to emerging drugs in vivo.