期刊
ACS NANO
卷 5, 期 11, 页码 8640-8648出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn2022149
关键词
nanosphere; endocytosis; neuron; polyethylenimine; multimodal imaging
类别
资金
- Australian Research Council (ARC)
- National Health & Medical Research Council (NHMRC) of Australia
- Perpetual (Philanthropy Australia)
- National Science Foundation [CBET-0756457]
- Australian Research Council Nanotechnology Network (ARCNN)
- University Government
- State Government
- Commonwealth Government
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [0756457] Funding Source: National Science Foundation
Polymer nanoparticles are widely used as a highly generalizable tool to entrap a range of different drugs for controlled or site-specific release. However, despite numerous studies examining the kinetics of controlled release, the biological behavior of such nanoparticles remains poorly understood, particularly with respect to endocytosis and intracellular trafficking. We synthesized polyethylenimine-decorated polymer nanospheres (ca 100-250 nm) of the type commonly used for drug release and used correlated electron microscopy, fluorescence spectroscopy and microscopy, and relaxometry to track endocytosis in neural cells. These capabilities provide insight into how polyethylenimine mediates the entry of nanoparticles into neural cells and show that polymer nanosphere uptake Involves three distinct steps, namely, plasma membrane attachment, fluid-phase as well as dathrin- and caveolin-independent endocytosis, and progressive accumulation in membrane-bound intracellular vesicles. These findings provide detailed insight into how the Intracellular delivery of nanoparticles is mediated by polyethylenimine, which is presently the most commonly used nonviral gene transfer agent This fundamental knowledge may also assist in the preparation of next-generation nonviral vectors.
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