期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 10, 期 2, 页码 339-348出版社
ELSEVIER
DOI: 10.1016/j.nano.2013.08.013
关键词
Mathematical model; Polymersome; Data fitting; Stochastic model; Endocytosis
资金
- Engineering and Physical Sciences Research Council, UK
- Yorkshire Cancer Research (5300), UK
- Engineering and Physical Sciences Research Council [EP/I010378/1] Funding Source: researchfish
- EPSRC [EP/I010378/1] Funding Source: UKRI
This study is motivated by understanding and controlling the key physical properties underlying internalisation of nano drug delivery. We consider the internalisation of specific nanometre size delivery vehicles, comprised of self-assembling amphiphilic block copolymers, called polymersomes that have the potential to specifically deliver anticancer therapeutics to tumour cells. The possible benefits of targeted polymersome drug delivery include reduced off-target toxic effects in healthy tissue and increased drug uptake by diseased tissue. Through a combination of in vitro experimentation and mathematical modelling, we develop a validated model of nanoparticle uptake by cells via the clathrin-mediated endocytotic pathway, incorporating receptor binding, clustering and recycling. The model predicts how the characteristics of receptor targeting, and the size and concentration of polymersomes alter uptake by tumour cells. The number of receptors per cell was identified as being the dominant mechanism accounting for the difference between cell types in polymersome uptake rate. (C) 2014 Elsevier Inc. All rights reserved.
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