Molecular Simulations of MOF Nanoparticles for Drug Delivery
: (Alternative Format Thesis)

  • Megan Thompson

Student thesis: Doctoral ThesisPhD


Metal-organic framework (MOF) nanoparticles are highly promising drug delivery carriers for chemotherapy due to their tailorable properties, biocompatibility and responsiveness to external stimuli. However, MOFs are typically characterised as infinite repeating crystals, and there is limited thermodynamic insight as to how the properties and performance of a MOF change as a function of its particle size. It is also not clear what properties are ideal for drug delivery, or what simulation methods should be used to best mimic drug uptake and delivery experiments.
In this thesis, molecular simulations were used to elucidate the particle-size influence on guest-molecule adsorption and induced framework flexibility in a flexible MOF, DUT-8(Ni), with various external surface functionalities. Standard and novel simulation techniques were also used to model the uptake and release of cisplatin (a chemotherapy drug) inside biocompatible MOFs UiO-66 and UiO-66(NH¬2) and compared to experimental results to test the advantages and limitations of each method. The simulation methods were finally used to test property – performance relationships in a series of biocompatible and pH sensitive MOFs as cisplatin delivery carriers, to pinpoint a selection criterion for MOFs used in further cancer-treatment research.
Overall, the external surface is not important for simulations in which the results mainly depend on the non-bonded interactions because the influence of the external surface on interaction energies is short-ranged. However, the external surface significantly contributes to the internal energy of the framework, hence it is important when characterising a MOF’s structural responses to external stimuli. Experimental drug uptake and delivery is carried out in aqueous solution. Simulations with and without water show that the non-solvated models can be misleading, and it is therefore crucial to understand the limitations of solvent free models whenever they are applied in drug delivery research. Finally, simulations of cisplatin uptake and release in potential MOF carriers show that wide pores interconnected by large windows will enhance drug molecule uptake from solution, which relies on the accessible pore volume and the driving force / energy barriers associated with uptake. Retention can be enhanced by creating large diffusion energy barriers. This can be achieved by functionalising the framework’s channels to get strong, dispersed adsorption sites, or by reducing the pore-window size, however the latter will also compromise drug-molecule uptake.
Date of Award28 Apr 2021
Original languageEnglish
Awarding Institution
  • University of Bath
SupervisorTina Düren (Supervisor) & Matthew Lennox (Supervisor)


  • MOF
  • Molecular Simulations
  • drug delivery

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