Recent Advances in Micro/Nanoneedle Arrays Mediated Intracellular Delivery of Biomacromolecules In Vitro and In Vivo

Intracellular delivery of biomacromolecules is critical for advancements in cell-based therapy, genome editing, regenerative medicine, and basic biological research. Recent developments in vertically aligned micro/nanoneedle arrays (MNNs) have shown significant promise for localized and controlled intracellular delivery by efficiently overcoming biological barriers to access the cytosol. Progress in both in vitro and in vivo applications reflects the potential of MNNs to transition from proof-of-concept to therapeutic tools. This review systematically summarizes recent advancements in both domains, highlighting MNNs as highly efficient, universal, and scalable vehicles. The discussion begins by detailing the innovative materials and structural features that enhance their delivery capabilities. This is followed by an exploration of how varying material and structural characteristics, surface chemistry, and external forces facilitate penetration across cellular barriers, alongside recent breakthroughs in understanding the debated mechanisms underlying MNNs-mediated intracellular delivery. Additionally, the interactions between engineered MNNs and dynamic tissue barriers, analyzing their role in facilitating macromolecular delivery across cellular barriers in vivo, are discussed. Finally, a brief overview of existing challenges and future prospects concerning improvements in MNNs-mediated intracellular delivery in preclinical applications is provided. This review aims to bridge micro/nanotechnology and cell biology, advancing laboratory research toward practical applications in life sciences.