Microinvasive Deployment and Fate-Determination of Functional, Engineered Nanoparticles in Central Nervous System

Abstract

Functionalized nanoparticles enable wireless, cell-specific neuromodulation by converting external physical fields into optical, thermal, electrical, or chemical stimuli. This capability presents unprecedented opportunities for neural circuit mapping and precise therapeutic interventions in neurological and psychiatric disorders. However, achieving minimally invasive, efficient, and accurately targeted nanoparticle delivery, coupled with controllable retention and clearance kinetics, remains challenging. Here, we first systematically review the primary strategies for deploying nanoparticles in the brain, with a particular focus on minimally invasive and precise deployment approaches that leverage external physical field interventions to overcome the blood-brain barrier. Next, we critically summarize the key physical factors governing nanoparticle transport across the blood-brain barrier. Additionally, we outline nanoparticle clearance pathways in the brain and discuss the primary determinants influencing nanoparticle fate. Finally, we outline outstanding challenges and propose future research directions toward reliable, highly controllable nanoparticle deployment within the nervous system.