Nanomedicine Directs Neuronal Differentiation of Neural Stem Cells via Silencing Long Noncoding RNA for Stroke Therapy

Transplantation of neural stem cells (NSCs) is a promising treatment paradigm to replace lost neurons and reconstruct the damaged neural circuit after ischemic stroke. However, most transplanted NSCs often differentiate into astrocytes rather than functional neurons, and the poor neuronal differentiation adversely affects the therapeutic outcome of NSCs and limits their clinical translation for stroke therapy. Herein, a theranostic nanomedicine is developed to codeliver superparamagnetic iron oxide nanoparticles (SPIO) and small interfering RNA/antisense oligonucleotides (siRNA/ASO) against Pnky long noncoding RNA (lncRNA) into NSCs. This nanomedicine not only directs neuronal differentiation of NSCs through silencing the Pnky lncRNA but also allows an in vivo tracking of NSCs with magnetic resonance imaging. The enhanced neuronal differentiation of NSCs significantly improved the structural and functional recovery of the damaged brain after a stroke. The results demonstrate the great potential of the multifunctional nanomedicine targeting lncRNA to enhance stem cell-based therapies for a stroke.