|ZFIN ID: ZDB-PUB-191003-6|
Nanoparticle-mediated delivery of siRNA into zebrafish heart: a cell-level investigation on the biodistribution and gene silencing effects
Wang, F., Wang, X., Gao, L., Meng, L.Y., Xie, J.M., Xiong, J.W., Luo, Y.
|Source:||Nanoscale 11(39): 18052-18064 (Journal)|
|Registered Authors:||Xiong, Jing-Wei|
|PubMed:||31576876 Full text @ Nanoscale|
Wang, F., Wang, X., Gao, L., Meng, L.Y., Xie, J.M., Xiong, J.W., Luo, Y. (2019) Nanoparticle-mediated delivery of siRNA into zebrafish heart: a cell-level investigation on the biodistribution and gene silencing effects. Nanoscale. 11(39):18052-18064.
ABSTRACTNanomaterials hold promise for the delivery of nucleic acids to facilitate gene therapy in cardiac diseases. However, as much of the in vivo study of nanomaterials was conducted via the "trial and error" method, the understanding of the nanomaterial-mediated delivery in cardiac tissue was limited to the gross efficiency in manipulating the gene expression while little was known about the delivery process and mechanism in particular at the cell level. In this study, small interfering RNA (siRNA) nanoparticles formulated with a polyamidoamine (PAMAM) nanomaterial were applied to the injured heart of zebrafish. The distribution of nanoparticles in cardiomyocytes, endothelial cells, macrophages and leukocytes was quantitatively analyzed with precision at the cell level by using transgenic models. Based on the distribution characteristics, gene silencing effects in a specific group of cells were analyzed to illustrate how siRNA nanoparticles could get potent gene silencing in different cells in vivo. The results elucidated the heterogeneous distribution of siRNA nanoparticles and how nanoparticles could be efficient despite the significant difference in cellular uptake efficiency in different cells. It demonstrated a paradigm and the need to decouple cellular processes to understand nanoparticle-mediated delivery in complex tissue and the investigation/methodology may lead to important information to guide the design of advanced targeted drug-delivery systems in heart.