Unit:
Κατεύθυνση ΒιοπληροφορικήΠληροφορική
Author:
Karathanou Konstantina
Supervisors info:
Δρ. Ζωή Κούρνια, Ερευνήτρια Γ’, Ίδρυμα Ιατροβιολογικών Ερευνών Ακαδημίας Αθηνών (ΙΙΒΕΑΑ)
Original Title:
Modeling and simulations of functionalized magnetic nanoparticles as drug delivery systems
Translated title:
Modeling and simulations of functionalized magnetic nanoparticles as drug delivery systems
Summary:
Nanoparticles (NPs) as drug delivery systems are engineered technologies for the delivery of therapeutic agents to their targets in a controlled manner and have shown significant potential to be employed in cancer treatment, with the aim to improve the biodistribution of cancer drugs. Magnetic nanoparticles (MNPs) are a class of nanoparticles, which can be manipulated using magnetic field gradients in order to reach the target site of interest and deliver the drug faster and more efficiently. Common MNPs consist of biocompatible iron oxide MNPs such as magnetite (Fe3O4) and its oxidized form maghemite (γ-Fe2O3) with proper surface architecture and conjugated targeting ligands/proteins.
A first consideration in assessing MNP toxicity as well as efficiency of translocation in a cell is the interaction of the MNP with the cell membrane. In the present thesis, computational approaches were used for the construction of functionalized magnetite MNPs of different shape, size, and surface chemistry. Subsequently, Molecular Dynamics (MD) simulations were performed to investigate the MNP in contact with a model cell membrane in order to gain insights into the physicochemical properties that govern the interactions between different classes of MNPs and the membrane.
Initially, a generic code that builds the model of the NP core of a given size and surface architecture was developed. The growing planes of the Fe3O4 crystal, which are analogous to the minimum surface energies, were used to extend the size and shape of the NP. This approach was generalized by developing an algorithm that constructs different crystal morphologies for a given crystal based on its preferred growing planes, the Miller indices and a user-defined size of the crystal. Subsequently, another algorithm was developed to attach polyvinyl alcohol (PVA) and polyarabic acid (ARA) ligands to the Fe3O4 MNP core. A dipalmitoylphosphatidylcholine (DPPC) lipid bilayer was then built as a model cell membrane. Finally, the two model MNPs were placed in the water phase of the lipid bilayer and atomistic MD simulations were performed in order to describe the nanoparticle-membrane interactions in atomic-level detail.
The results from our simulations were further compared to available experimental data from our collaborators and conclusions were drawn for the distinct interactions between the different ligand coating of the NP and the model cell membrane.
Main subject category:
Technology - Computer science
Keywords:
nanoparticles, drug delivery systems, magnetite, molecular dynamics, atomistic simulations
Number of references:
201
