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New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

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Nội dung chi tiết: New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

MONASH UniversityNew polymeric nanoparticles to interrupt the ROS- and RNS-derived misregulation of cellsVan Nam DAOBPharm. (Hons). MPharmSc.A thesis

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells submitted for the degree of Doctor of Philosophy atMonash University in 2021Faculty of Pharmacy and Pharmaceutical SciencesMONASH UniversityNew polym

eric nanoparticles to interrupt the ROS- and RNS- derived misregulation of cellsVan Nam DAOBPharm. (Hons)r MPharmSc.Supervisors:Dr. John Quinn Dr. Mic New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

hael Whittaker A/ Prof. Erica SloanPanel members:Dr. Angus Johnston Dr. Betty Exintaris Dr. Daniel PooleA thesis submitted for the degree of Doctor of

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

Philosophy at Monash University in 2021Faculty of Pharmacy and Pharmaceutical SciencesCopyright notice©Van Nam DAO (2021).I certify that I have made

MONASH UniversityNew polymeric nanoparticles to interrupt the ROS- and RNS-derived misregulation of cellsVan Nam DAOBPharm. (Hons). MPharmSc.A thesis

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells to my work without the owner's permission.AbstractReactive oxygen species (ROS) and reactive nitrogen species (RNS) have critical roles in various bio

logical processes and signaling pathways. Moreover, perturbations in ROS and RNS levels often occur with changes in metabolism and health disorders. T New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

he application of scavengers, which are capable of reducing ROS and RNS levels, could potentially protect cells from being damaged by these reactive m

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

olecules. Further, manipulating ROS and RNS levels can also interrupt downstream communication between impaired cells and other surrounding tissue, as

MONASH UniversityNew polymeric nanoparticles to interrupt the ROS- and RNS-derived misregulation of cellsVan Nam DAOBPharm. (Hons). MPharmSc.A thesis

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells ulfide compounds that mimic cellular defense pathways and offer inherent ROS scavenging activities is another potential approach to alleviate ROS leve

ls. Further, the recent development of nanomedicine has enabled researchers to address issues associated with small molecular drugs, such as nonspecif New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

ic binding, low tissue permeation and short retention time.In this thesis, polymer-based scavengers for ROS and RNS have been developed which i) explo

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

it advanced polymer design, li) contain novel reactive moieties, lii) scavenge ROS and/or RNS intracellularly, and iv) confer downstream effects in th

MONASH UniversityNew polymeric nanoparticles to interrupt the ROS- and RNS-derived misregulation of cellsVan Nam DAOBPharm. (Hons). MPharmSc.A thesis

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells cal systems Recent advances in development of hydrogen sulfide and persulfide donors, as well as macromolecular ROS/RNS scavengers, are also described

. Subsequently, in a series of experimental chapters, data are presented about four main categories of materials that have been developed: linear and New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

brush polymers bearing trisulfide moieties for releasing hydrogen sulfide and persulfides (Chapter 2 and Chapter 3). polymer carriers for delivering W

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

-acetyl L-cysteine intracellularly (Chapter 4). star polymers for conjugating a small molecule antioxidant (TEMPO) (Chapter 5) and nitric oxide scaven

MONASH UniversityNew polymeric nanoparticles to interrupt the ROS- and RNS-derived misregulation of cellsVan Nam DAOBPharm. (Hons). MPharmSc.A thesis

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells rther, the impact of the synthesised materials on cell viability, and their biological performance, i.e. ROS -RNS scavenging ability, were evaluated o

n several models, including a naturally elevated ROS level model which can simulate TME communication (a co-culture of fibroblasts and breast cancer c New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

ells, Chapters 2. 4 and 5). an externally stimulated oxidative stress model (HEK293 ưeated with H?o?. Chapter 3). and a naturally elevated RNS model (

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

activated primary and cell line macrophages.Chapter 6) Where appropriate, other intracellular behaviour of the synthesised compounds was evaluated, in

MONASH UniversityNew polymeric nanoparticles to interrupt the ROS- and RNS-derived misregulation of cellsVan Nam DAOBPharm. (Hons). MPharmSc.A thesis

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells ymer treatment were also examined, including ROS-associated cellular changes (collagen-1 and F-actm expression. Chapter 2). NO-llnked phagocytosis act

ivity (Chaptei 6), or mitochondrial functions (superoxide anion production and co-localisation. Chapter 5). The materials developed in the thesis repr New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

esent novel entities for manipulating cellular signaling pathways, and are potentially applicable to diverse fields including the pharmaceutical, poly

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

mer and material sciences, as well as oncology and pharmacologyPublications during enrolment1. Urquhart MC. Dao NV Ercole F. Boyd BJ, Davis TP, Whitta

MONASH UniversityNew polymeric nanoparticles to interrupt the ROS- and RNS-derived misregulation of cellsVan Nam DAOBPharm. (Hons). MPharmSc.A thesis

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells tt. 2020:9(4 ):553-7.2 Dao NV. Ercole F. Kaminskas LM, Davis TP. Sloan EK. Whittaker MR. et al Trisulfide-bearing PEG brush polymers donate hydrogen s

ulfide and ameliorate cellular oxidative stress. Biomacromolecules. 2020 21(12):5292-305.3. Dao NV. Ercole F. Urquhart MC. Kaminskas LM. Nowell CJ. Da New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

vis TP. et al. Trisulfide linked cholesteryl PEG conjugate attenuates intracellular ROS and collagen-1 production in a breast cancer co-culture model.

New polymeric nanoparticles to interrupt the ros and rns derived misregulation of cells

Biomaterials Science. 2021. DOI 10 1039/D0BM01544J

MONASH UniversityNew polymeric nanoparticles to interrupt the ROS- and RNS-derived misregulation of cellsVan Nam DAOBPharm. (Hons). MPharmSc.A thesis

MONASH UniversityNew polymeric nanoparticles to interrupt the ROS- and RNS-derived misregulation of cellsVan Nam DAOBPharm. (Hons). MPharmSc.A thesis

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