A mathematical investigation into the uptake kinetics of nanoparticles in vitro

West, Hannah and Roberts, Fiona and Sweeney, Paul and Walker-Samuel, Simon and Leedale, Joseph and Colley, Helen and Murdoch, Craig and Shipley, Rebecca J. and Webb, Steven (2021) A mathematical investigation into the uptake kinetics of nanoparticles in vitro. PLoS ONE, 16 (7). e0254208. ISSN 1932-6203 (https://doi.org/10.1371/journal.pone.0254208)

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Abstract

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.

  • Item type:Article
    ID code:78001
    Dates:
    Date
    Event
    22 July 2021
    Published
    23 June 2021
    Accepted
    7 December 2020
    Submitted
    Subjects:Science > Mathematics
    Department:Faculty of Science > Mathematics and Statistics
    Depositing user: Pure Administrator
    Date deposited:04 Oct 2021 14:35
    Last modified:11 Nov 2024 13:15
    URI:https://strathprints.strath.ac.uk/id/eprint/78001
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