Content:
In this thesis, the main objective is to understand the relationship between the physicochemical properties and the biological activities of nanoparticles based on the self-assembled block glycopolymers and the zwitterionic poly(2-methacryloyloxyethyl phosphorycholine) (MPC) block copolymers. In addition to the physicochemical properties of nanoparticles such as size, shape, and surface chemistry, drug effects on the nanoparticles' structure and function are investigated. Due to the interaction between the hydrophobic drugs and hydrophilic polymers, hydrophobic drugs might unexpectedly locate in the hydrophilic environment (hydrophilic shell) which can not only induce morphological transitions, but also influence the internal structure of nanoparticles, such as hydration and grafting density. These factors affect the cellular uptake in vitro. Generally, higher hydration of nanoparticles' shells is correlated with an enhanced cellular uptake in MCF-7 cells, MDA-MB-231 cells, and RAW 264.7 cells due to the bioactive group more efficiently contacting to cells in a water environment.Moreover, nanoparticles with higher grafting density polymers suggest a lower cellular uptake due to their increased ability to adsorb protein, and the adsorbed protein not only influences the internal structure change (e.g. thickness of shell and core radius) but also induces an overall shape transition from sphere to oblate. All these factors may lead to lower cellular uptake. Additionally, higher grafting density does not afford an enhanced cellular uptake when the nanoparticles do not adsorb proteins, such as the zwitterionic poly(2-methacryloyloxyethyl phosphorycholine) (MPC) nanoparticles. Small angle X-ray scattering (SAXS) and small angle neutron scattering (SANS), with the help of DLS and TEM, play important roles in not only characterizing the size and shape, but also providing information on the internal structure of nanoparticles (e.g. hydration, aggregation number, and grafting density). In this thesis, small angle scattering (SAS) techniques are employed to investigate the relationship between the physicochemical properties of nanoparticles and their biological activities for better drug delivery vehicles.
Note:
Dissertation University of New South Wales. Chemistry 2019
Language:
English
Bookmarklink