Hou Yannan, Chen Meizi, Yang Letao, Lee Ki-Bum
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States.
Shanghai Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry of Education, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Nano Lett. 2025 Jul 2;25(26):10402-10411. doi: 10.1021/acs.nanolett.5c01840. Epub 2025 Jun 10.
Induced pluripotent stem cells (iPSCs) offer immense potential for treating central nervous system (CNS) disorders and injuries. However, the lack of highly sensitive, selective, and noninvasive biosensors for real-time monitoring of iPSC neuronal differentiation remains a critical barrier. In this work, we introduce a gold nanorod-based metal-enhanced molecular beacon (MEMB) nanobiosensor for the noninvasive, real-time detection of intracellular miRNA-124, a key biomarker for neuronal differentiation in human iPSC-derived neural stem cells. Designed through finite-difference time-domain (FDTD) simulations and experimentally validated for optimized localized surface plasmon resonance (LSPR) properties, MEMB nanobiosensors achieved picomolar-level sensitivity and single-mismatch selectivity toward miRNA-124 detection, along with great biocompatibility demonstrated by live-cell assays. Collectively, the MEMB platform provides a robust analytical tool for in-depth investigations of molecular and genetic regulatory networks during iPSC neuronal differentiation in a nondestructive manner, paving the way toward safer, more efficient, and better-characterized iPSC-derived cell therapies for CNS diseases and injuries.
诱导多能干细胞（iPSC）在治疗中枢神经系统（CNS）疾病和损伤方面具有巨大潜力。然而，缺乏用于实时监测iPSC神经元分化的高度灵敏、选择性和非侵入性生物传感器仍然是一个关键障碍。在这项工作中，我们引入了一种基于金纳米棒的金属增强分子信标（MEMB）纳米生物传感器，用于非侵入性实时检测细胞内miRNA-124，这是人类iPSC来源神经干细胞中神经元分化的关键生物标志物。通过时域有限差分（FDTD）模拟设计并通过实验验证了其优化的局域表面等离子体共振（LSPR）特性，MEMB纳米生物传感器对miRNA-124检测实现了皮摩尔级灵敏度和单碱基错配选择性，活细胞实验也证明了其良好的生物相容性。总体而言，MEMB平台提供了一种强大的分析工具，以无损方式深入研究iPSC神经元分化过程中的分子和遗传调控网络，为更安全、高效且特性更明确的iPSC来源细胞治疗CNS疾病和损伤铺平了道路。
