A mathematical investigation into the uptake kinetics of nanoparticles in vitro.

Nanoparticles have the potential to increase the efficacy of anticancer drugs whilst reducing off-target side effects. However, there remain uncertainties regarding the cellular uptake kinetics of nanoparticles which could have implications for nanoparticle design and delivery. Polymersomes are nano...

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Autores principales:	Hannah West, Fiona Roberts, Paul Sweeney, Simon Walker-Samuel, Joseph Leedale, Helen Colley, Craig Murdoch, Rebecca J Shipley, Steven Webb
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/81b955807a9144d8933128dc95e0bd7e
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spelling	oai:doaj.org-article:81b955807a9144d8933128dc95e0bd7e2021-12-02T20:06:36ZA mathematical investigation into the uptake kinetics of nanoparticles in vitro.1932-620310.1371/journal.pone.0254208https://doaj.org/article/81b955807a9144d8933128dc95e0bd7e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254208https://doaj.org/toc/1932-6203Nanoparticles have the potential to increase the efficacy of anticancer drugs whilst reducing off-target side effects. However, there remain uncertainties regarding the cellular uptake kinetics of nanoparticles which could have implications for nanoparticle design and delivery. Polymersomes are nanoparticle candidates for cancer therapy which encapsulate chemotherapy drugs. Here we develop a mathematical model to simulate the uptake of polymersomes via endocytosis, a process by which polymersomes bind to the cell surface before becoming internalised by the cell where they then break down, releasing their contents which could include chemotherapy drugs. We focus on two in vitro configurations relevant to the testing and development of cancer therapies: a well-mixed culture model and a tumour spheroid setup. Our mathematical model of the well-mixed culture model comprises a set of coupled ordinary differential equations for the unbound and bound polymersomes and associated binding dynamics. Using a singular perturbation analysis we identify an optimal number of ligands on the polymersome surface which maximises internalised polymersomes and thus intracellular chemotherapy drug concentration. In our mathematical model of the spheroid, a multiphase system of partial differential equations is developed to describe the spatial and temporal distribution of bound and unbound polymersomes via advection and diffusion, alongside oxygen, tumour growth, cell proliferation and viability. Consistent with experimental observations, the model predicts the evolution of oxygen gradients leading to a necrotic core. We investigate the impact of two different internalisation functions on spheroid growth, a constant and a bond dependent function. It was found that the constant function yields faster uptake and therefore chemotherapy delivery. We also show how various parameters, such as spheroid permeability, lead to travelling wave or steady-state solutions.Hannah WestFiona RobertsPaul SweeneySimon Walker-SamuelJoseph LeedaleHelen ColleyCraig MurdochRebecca J ShipleySteven WebbPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254208 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hannah West Fiona Roberts Paul Sweeney Simon Walker-Samuel Joseph Leedale Helen Colley Craig Murdoch Rebecca J Shipley Steven Webb A mathematical investigation into the uptake kinetics of nanoparticles in vitro.
description	Nanoparticles have the potential to increase the efficacy of anticancer drugs whilst reducing off-target side effects. However, there remain uncertainties regarding the cellular uptake kinetics of nanoparticles which could have implications for nanoparticle design and delivery. Polymersomes are nanoparticle candidates for cancer therapy which encapsulate chemotherapy drugs. Here we develop a mathematical model to simulate the uptake of polymersomes via endocytosis, a process by which polymersomes bind to the cell surface before becoming internalised by the cell where they then break down, releasing their contents which could include chemotherapy drugs. We focus on two in vitro configurations relevant to the testing and development of cancer therapies: a well-mixed culture model and a tumour spheroid setup. Our mathematical model of the well-mixed culture model comprises a set of coupled ordinary differential equations for the unbound and bound polymersomes and associated binding dynamics. Using a singular perturbation analysis we identify an optimal number of ligands on the polymersome surface which maximises internalised polymersomes and thus intracellular chemotherapy drug concentration. In our mathematical model of the spheroid, a multiphase system of partial differential equations is developed to describe the spatial and temporal distribution of bound and unbound polymersomes via advection and diffusion, alongside oxygen, tumour growth, cell proliferation and viability. Consistent with experimental observations, the model predicts the evolution of oxygen gradients leading to a necrotic core. We investigate the impact of two different internalisation functions on spheroid growth, a constant and a bond dependent function. It was found that the constant function yields faster uptake and therefore chemotherapy delivery. We also show how various parameters, such as spheroid permeability, lead to travelling wave or steady-state solutions.
format	article
author	Hannah West Fiona Roberts Paul Sweeney Simon Walker-Samuel Joseph Leedale Helen Colley Craig Murdoch Rebecca J Shipley Steven Webb
author_facet	Hannah West Fiona Roberts Paul Sweeney Simon Walker-Samuel Joseph Leedale Helen Colley Craig Murdoch Rebecca J Shipley Steven Webb
author_sort	Hannah West
title	A mathematical investigation into the uptake kinetics of nanoparticles in vitro.
title_short	A mathematical investigation into the uptake kinetics of nanoparticles in vitro.
title_full	A mathematical investigation into the uptake kinetics of nanoparticles in vitro.
title_fullStr	A mathematical investigation into the uptake kinetics of nanoparticles in vitro.
title_full_unstemmed	A mathematical investigation into the uptake kinetics of nanoparticles in vitro.
title_sort	mathematical investigation into the uptake kinetics of nanoparticles in vitro.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/81b955807a9144d8933128dc95e0bd7e
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A mathematical investigation into the uptake kinetics of nanoparticles in vitro.

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