Development of polymer-coated upconverting nanoparticles for drug delivery

dc.contributor.advisor Stenzel, Martina en_US Zhang, Lin en_US 2022-03-15T08:53:28Z 2022-03-15T08:53:28Z 2021 en_US
dc.description.abstract In this thesis, the main objective was to develop polymer-coated upconversion nanoparticles (UCNPs) for anticancer drug delivery. The ability of UCNPs to convert low energy near-infrared (NIR) light into high energy visible-ultraviolet light has resulted in its development as novel contrast agents for biomedical imaging-guided drug delivery. However, UCNPs succumb to poor colloidal stability in aqueous media, which can be alleviated by surface modifications. Adding a polymer cloak to the nanoparticle would ensure enhanced stability in biological media, playing an instrumental role in its biomedical applications. Firstly, poly(poly(ethylene glycol)methyl ether methacrylate)-block-poly(ethylene glycol methacrylate phosphate) (PPEGMEMAn-b-PEGMP3) polymers, where n = 26, 38 and 80, were prepared and attached to the UCNPs. The relationship between the length and grafting density of the polymer shell were then investigated for their effects on the physicochemical and biological properties of these core-shell UCNPs. The results showed that UCNPs coated with the longest PPEGMEMA chain, grafted at low brush density, were able to reduce the formation of the protein corona in vitro and in vivo whilst also showing the brightest upconversion luminescence in the solid-state. Secondly, the optimized chain length polymer was further introduced in polymethacrylic acid groups to attach the anticancer drug doxorubicin·HCl (DOX). To study the effect of drug loading amount on the biological activity of nanoparticles, a tri-block terpolymer poly (poly (ethylene glycol) methyl ether methacrylate) block polymethacrylic acid block polyethylene glycol methacrylate phosphate (PPEGMEMA80-b-PMAA20-b-PEGMP3) was synthesized to coat UCNPs and loaded different amounts of DOX (DOX-0 (0%), DOX-1 (1.32%), DOX-2 (4.06%), and DOX-3 (8.30%)). This study found that the effect of DOX loading on the biological behaviour of UCNPs was dominated by polymer shell hydration and protein corona. In addition to this, a particular protein corona was able to direct in vitro cellular association and in vivo biodistribution of the UCNPs. Finally, estrone ligand was introduced to PPEGMEMAx-b-PMAAy-b-PEGMP3 (x=7,15,33,80; y=16,20,18,18)-coated UCNPs with the expectation of enhancing the nanocarrier’s targeting ability towards estrogen receptor. In this study, the impact of the targeting ligand’s position, as well as PEGMEMA linker length, was studied for their effects on cellular uptake behaviour. The shortest polymer PPEGMEMA7-b-PMAA16-b-PEGMP3 appended with estrone at the end of the polymer chain was found to have the best cellular uptake behaviour in estrogen receptor α positive expression cell line MCF-7 and could efficiently improve the toxicity in estrogen receptor α positive expression cell lines and 3D spheroid model. en_US
dc.language English
dc.language.iso EN en_US
dc.publisher UNSW, Sydney en_US
dc.rights CC BY-NC-ND 3.0 en_US
dc.rights.uri en_US
dc.title Development of polymer-coated upconverting nanoparticles for drug delivery en_US
dc.type Thesis en_US
dcterms.accessRights open access
dcterms.rightsHolder Zhang, Lin
dspace.entity.type Publication en_US
unsw.accessRights.uri 2023-11-05 en_US
unsw.description.embargoNote Embargoed until 2023-11-05
unsw.relation.faculty Science
unsw.relation.originalPublicationAffiliation Zhang, Lin, School of Chemistry, Science, UNSW en_US
unsw.relation.originalPublicationAffiliation Stenzel, Martina, School of Chemistry, Science, UNSW en_US School of Chemistry *
unsw.thesis.degreetype PhD Doctorate en_US
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