Jin-Ho Lee,^†,‡,∥ Jin-Ha Choi,^†,‡,∥ Sy-Tsong Dean Chueng,^† Thanapat Pongkulapa,^† Letao Yang,^† Hyeon-Yeol Cho,^†,‡ Jeong-Woo Choi,^*,‡ and Ki-Bum Lee^*,†,§

^†Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, United States ^‡Department of Chemical and Biomolecular Engineering, Sogang University, Seoul 04107, Republic of Korea ^§Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea

^*Corresponding Authors

Author Contributions
^∥J.-H.L. and J.-H.C. contributed equally.

The full realization of stem cell-based treatments for neurodegenerative diseases requires precise control and characterization of stem cell fate. Herein, we report a multifunctional magneto-plasmonic nanorod (NR)-based detection platform to address the limitations associated with the current destructive characterization methods of stem cell neurogenesis. Exosomes and their inner contents have been discovered to play critical roles in cell–cell interactions and intrinsic cellular regulations and have received wide attention as next-generation biomarkers. Moreover, exosomal microRNAs (miRNA) also offer an essential avenue for nondestructive molecular analyses of cell cytoplasm components. To this end, our developed nondestructive, selective, and sensitive detection platform has (i) an immunomagnetic active component for exosome isolation and (ii) a plasmonic/metal-enhanced fluorescence component for sensitive exosomal miRNA detection to characterize stem cell differentiation. In a proof-of-concept demonstration, our multifunctional magneto-plasmonic NR successfully detected the expression level of miRNA-124 and characterized neurogenesis of human-induced pluripotent stem cell-derived neural stem cells in a nondestructive and efficient manner. Furthermore, we demonstrated the versatility and feasibility of our multifunctional magneto-plasmonic NRs by characterizing a heterogeneous population of neural cells in an ex vivo rodent model. Collectively, we believe our multifunctional magneto-plasmonic NR-based exosomal miRNA detection platform has a great potential to investigate the function of cell–cell interactions and intrinsic cellular regulators for controlling stem cell differentiation.

KEYWORDS: magneto-plasmonic nanorods, exosomal miRNAs, stem cells, neuronal differentiation, nondestructive characterization