Executive Summary : | Small molecule-based anti-cancer drugs have severe side effects, such as nausea, vomiting, and hair loss, and their non-targeted systemic distribution can significantly decrease the life quality of cancer patients. To address this issue, researchers are developing suitable drug delivery systems using polymeric carriers (10-200 nm). One such system is the self-assembly of amphiphilic polythiourethanes, which have better in vivo bioavailability, bio-distribution, and clearance ability than other hydrophilic linear polymers. Polythiourethanes have advantages such as H-bonding functionality along the chain, which can direct assembly rather than collapse due to the hydrophobic effect. During polymerization, free thiols can be used to couple hydrophobic groups, drugs, or crosslink the hydrophobic membrane, increasing the stability of the formed nano-aggregates. The interior of polymersomes can efficiently transport hydrophilic payloads, while hydrophobic drugs can be encapsulated in the membrane. Stimuli-responsive groups, such as reactive oxygen species (ROS), pH, and redox, can be incorporated to make the polymersomes degradable and release the loaded cargo at the target site on demand. Hydrophobic groups, such as phenyl, biphenyl, and alkyl chains, can be incorporated into the polythiourethane backbone, and their effect on nanoaggregate stability and loading capacity will be studied. Dendronized oligoglycerol-based amphiphilic graft-polythiourethane will be prepared by quenching the thiols with acid chlorides of corresponding dendrons, presenting targeting groups in a multivalent fashion outside the polymersomes. The optimal nanocarrier will be developed by studying the influence of hydrophobic groups on drug encapsulation. |