The Synthesis, Physicochemical Characterization and Biological Interactions of Polymer-Coated Nanoparticles

I-Chun Lin (2011). The Synthesis, Physicochemical Characterization and Biological Interactions of Polymer-Coated Nanoparticles PhD Thesis, School of Chemistry & Molecular Bioscience, The University of Queensland.

       
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Author I-Chun Lin
Thesis Title The Synthesis, Physicochemical Characterization and Biological Interactions of Polymer-Coated Nanoparticles
School, Centre or Institute School of Chemistry & Molecular Bioscience
Institution The University of Queensland
Publication date 2011-06
Thesis type PhD Thesis
Supervisor Professor Istvan Toth
Professor Michael Monteiro
Total pages 203
Total colour pages 39
Total black and white pages 164
Subjects 03 Chemical Sciences
Abstract/Summary The versatility in the synthesis of polymer nanocomposites has allowed researchers to tune the size, surface charge and their function for use in various biomedical applications. However the behaviours of these engineered nanomaterials in biological systems are still being elucidated. Due to the different physico-chemical properties and multifunctionality, nanoparticles may interact with various biological components causing different toxic/health concerns. With means to improve the efficiency and the performance of engineered nanoparticles, it is necessary to understand the interactions of nanoparticles in the biological systems. For this purpose, a library of polymer coated nanoparticles (gold and silica) was designed with different sizes (5 nm ~150 nm) and surface properties (hydrophilic/hydrophobic, postive, negative and neutral surface charge). The polymers used were prepared by RAFT-mediated polymerization and grafted onto the nanoparticle surface. Grafting of polymers made by RAFT onto gold nanoparticles (AuNPs) gave a densely packed polmyer shell as quantified by thermogravimetric analysis (TGA). In comparison, polymers were found to have low grafting densities on SiNPs. The grafting desnity for the majority of polymers on the AuNP surface was around 0.7 ~1.4 chains/nm2. With such high grafting densities, the surface properties and the size of these hybrid nanoparticles were the only contributing factors affecting their behaviour in the biological system. The surface properties of the nanoparticles were known to play a crucial role in their interaction with cells. The uptake and transport of the nanoparticles library were investigated using epithelial Caco-2 cells, which represented an excellent model to resemble the human intestinal epithelium. The modification of the nanoparticle with the positively charged polymers (PAEA-AuNPs) gave the greatest uptake due to its high affinity to the negatively charged cell membrane. Interestingly, the uptake efficiency for PNIPAM-AuNPs (neutral charged but becomes hydrophobic at 37 oC) was much greater than the negative and neutral AuNPs. It is believed that this is caused by the hydrophobic interactions with the cell membrane or the increase in nanoparticle size. Despite the high level of cellular uptake of the hydrophobic and postive charged AuNPs, the translocation of these nanoparticles across Caco-2 cell monolayers was low. Instead these particles were trapped inside endocytic vesicles or endosomes in the cytoplasm as shown by TEM. Only the neutral PDHA, PEG-AuNPs and negative charged PAA-AuNPs were able to transport thorugh the Caco-2 cell monolayer with higher efficiency. Smaller nanoparticles were also found to have a greater translocation across cell monolayers compared to larger nanoparticles. All polymer-coated AuNPs displayed a marked effect on the translocation of small molecules across the cellular monolayer. This suggested that all tested nanoparticles can loosen the paracellular tight junction joing individual cells. The resistance values (TEER) of monolayers decreased upon the opening of tight junctions but generally recovered 12 h after removal of the polymer-coated AuNPs. The mechanism of nanoparticle cellular transport was investigated by endocytosis inhibition test. Transport of nanoparticle through the cell monolayer involved both a transcellular or paracellular pathway. The endocytic uptake and transport of nanoparticles underwent either a microtubule-dependent or microtubule-independent mechanisms. An interesting finding was that neutral polymer coatings (PEG and PDHA) facilitated different types of endocytic transport. The majority of the polymer coated nanoparticles tested also showed no apparent signs of toxicity from the in vitro assays. In summary, this thesis detailed the synthesis of nanoparticles with controlled sizes and presented a practical approach to modify the surface properties of different nanoparticles with polymers. These studies have provided insights on the influence of nanoparticle surface properties on their cellular interaction and toxicity. While numerous studies have started to examine the effect of nanoparticles surface properties on their biological interactions, many challenges and mystery in this area of research still remains to be solved. This nanoparticle library could potentially help researchers to forecast the biological properties of novel pharmaceutically important nanomaterials, aiding in their future design and use.
Keyword nanoparticle
polymer synthesis
living radical polymerization (LRP)
Caco-2 Cell
Cellular interactions
Cell Uptake
Cell Transport
Endocytosis
Additional Notes Colour pages: 43-45, 47, 50, 52, 66, 72, 74-76, 85, 88-90, 108, 112-113, 131-132, 136-138, 145, 147, 152, 154, 159-160, 163, 165, 172, 174-175, 195-197, 201-202.

 
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Created: Mon, 31 Oct 2011, 14:43:29 EST by Mr I-chun Lin on behalf of Library - Information Access Service