Engineering Female Germline Stem Cells with Exocytotic Polymer Dots.

Germline stem cells (GSCs) are the only cell population capable of passing genetic information to offspring, making them attractive targets in reproductive biology and fertility research. However, it is generally more difficult to introduce exogenous biomolecules into GSCs than other cell types, impeding the exploration and manipulation of these cells for biomedical purposes. Herein, we develop semiconductor polymer dots (Pdots)-based nanocomplex Pdot-siRNA and achieve effective knockdown of target genes in FGSCs. We take advantage of high fluorescence brightness of Pdots for comprehensive investigation of their cellular uptake, intracellular trafficking and exocytosis in FGSCs. Importantly, Pdots show excellent biocompatibility and minimally disturb the differentiation of FGSCs. Intracellular Pdots escape from the lysosomes and undergo active exocytosis, which make them ideal nanocarriers for bioactive cargos. Moreover, Pdot-siRNA can penetrate into 3D ovarian organoids derived from FGSCs and down-regulate the expression levels of target genes. Our study investigates the interface between a type of theranostic nanoparticles and FGSCs for the first time and sheds lights on the manipulation and medical application of FGSCs. This article is protected by copyright. All rights reserved.