Red blood cells (RBCs) and the proteins within are crucial for oxygen and carbon dioxide transport, but challenges with their storage and supplementation have led to the development of artificial oxygen carriers (AOCs). These have included hemoglobin-based (HBOCs), iron(II)-porphyrin-based (IronpBOCs), and fluorinated-based oxygen carriers (FBOCs). While HBOCs and IronpBOCs mimic the oxygen binding properties of RBCs, their high porphyrin content can cause vasoconstriction. FBOCs, which absorb and release gas physically, have milder effects and are useful for organ perfusion, photodynamic therapy, and the treatment of carbon monoxide poisoning. However, FBOCs do demonstrate significant side effects, including immune responses, fluorine buildup, and long half-lives and instability. This study aims to develop a series of improved oxygen carriers using fluorine containing polymer-based systems that enhance stability and reduce fluorine accumulation. The first system we investigated were self-assembled fluorinated micelles and vesicles. Two systems were developed using monomers with either three or five fluorines per monomer were used to synthesise the target amphiphilic diblock polymers (3F-mPEG-b-PTF and 5F-mPEG-b-PPF). The polymers were synthesized using an atom transfer radical polymerization (ATRP) and a mPEG initiator. The diblock polymers were characterized by nuckear magnetic resonance (NMR), and fourier transform infrared spectroscopy (FTIR). Gel permeation chromatography (GPC) was also used to measure a relative molecular weight, which could be compared to the molecular weight calculated from 1H NMR. Critical aggregation concentrations (CAC) of the diblock polymers were determined using a pyrene methodology, which showed that polymers with higher degree of polymerization (DP) for the fluorinated segments led to lower CAC values. The diblock polymers formed fluorine cored micelles (3F-micelle 15 and 5F-micelle 16), and a vesicle (5F-vesicle 17) when the 3F-mPEG-b-PTF25 6, 5F-mPEG-b-PPF17 10, and 5F-mPEG-b-PPF25 11 diblock polymers were dissolved in water. The oxygen-carrying properties of the micelles and vesicles were measured using a dissolved oxygen sensor, revealing that the 5F-micelle 16 exhibited a 13% higher level of dissolved oxygen than the 3F�micelle 15, and 21% higher than that of water. The 5F-vesicle 17, had the best oxygen binding results and demonstrated a 53%, 35%, and 22% higher level of oxygen solubility than water, the 3F-micelle 15, and the 5F-micelle 16, respectively. However, the vesicles were not particularly stable, and fractured systems were observed in TEM. To increase stability, and generate larger particles, we developed a new system based on polyion complexs. The systems utilized a polycation fluorine containing amphiphilic polymer and porphyrin anion as the crosslinker. Two polycation polymers, mPEG-(PDE30-r-PTF28) and mPEG-(PDE50-r-PPF45), were synthesized, along with a porphyrin functionalized with carboxyl groups. The structures were confirmed using 1H, 13C, 19F NMR, Mass spectrum, GPC, and FTIR. The polyion complexes were created via the thin film hydration method, with specific polycation/porphyrin ratios being investigated for each complex. The sizes of the non-complexed polymers were less than 100 nm, while the poly-ion complexes had diameters ranging from 240 nm to 565 nm. The oxygen-carrying properties were measured using a dissolved oxygen sensor. The results showed a significant increase in oxygen binding for the TCPP-crosslinked mPEG-(PDE30-r�PTF28) and TCPP-crosslinked mPEG-(PDE50-r-PPF45) polyions. Improvements in oxygen solubility of 110% and 226% were observed when compared to pure water (relative to TCPP�crosslinked mPEG-(PDE30-r-PTF28) and TCPP-crosslinked mPEG-(PDE50-r-PPF45) respectively). These improvements in oxygen solubility were attributed to the large fluorine�rich environment within these larger particles. An alternative strategy to improve nanoparticle stability was developed using core-shell nano-emulsions (CSNPs) was also explored. A pre�polymerization study successfully demonstrated the feasibility of forming CSNPs using nanoparticle synthesized by emulsion polymerization of a TMS monomer and a TFEMA monomer. This was followed by the synthesis of functionalised CSNPs, whose structures were confirmed using FTIR, elemental analysis, and 1H NMR. However, secondary nucleation led to the formation of large, non-spherical particles, especially in the CSNPs@OH samples, with sizes ranging from 290 nm to 390 nm, as observed by TEM. The oxygen-carrying properties of these nanoparticles showed limited improvement at low concentrations, with oxygen release half-lives near 0% for CSNPs@OH-1, 17% for CSNPs@OH-2, and 20% for CSNPs@OH-3, compared to pure water. As the concentration increased, oxygen release improved significantly: for CSNPs@OH-1, 51 minutes (26% increase); for CSNPs@OH-2, 95 minutes (110% increase); and for CSNPs@OH-3, 118 minutes (160% increase). In experiments using an ethanol/water solvent mixture, aggregation was observed in CSNPs@OH-M-1, and spherical and raspberry-like nanoparticles appeared in CSNPs@OH-M-2 and CSNPs@OH-M-3, respectively. However, aggregation in these samples led to overestimation of their oxygen release half-life. A comparison between the best samples prepared in different chapters exhibited that the TCPP-crosslinked mPEG-(PDE50-r-PPF45) was the most valuable sample in this project.
