Exploring UCST behaviour for the design of degradable polymeric drug nanocarriers

Cancer is still a leading cause of dead and the use of chemotherapy is prone to severe systemic side effects. By consequence, there is a clear need for more efficient strategies for the delivery of anti-cancer drugs that result in low exposure to healthy cells and tissues but improved delivery of the drug to cancer cells. In view of this, the main objective of this project is to devise a fully synthetic supramolecular approach that allows for efficient anti-cancer drug formulation and cancer cell targeting. To address this challenge, we will explore a novel class of degradable polymers that exhibit Upper Critical Solution Temperature (UCST) behaviour. Such polymers are soluble above a critical temperature, but precipitate from solution (due to hydrogen bond formation) below this temperature. In response to side-chain hydrolysis, these polymers lose their UCST behaviour and become fully water-soluble, irrespective of temperature. The use of this phenomenon will be explored for the design of drug nanocarriers based on block copolymer that self-assemble at physiological temperature into micellar nanoparticles due to the UCST effect. Core-crosslinking and covalent drug ligation will be performed to confer stability of the nanocarriers in complex physiological media and to allow for nanoparticle decomposition and drug release in response to the acidic milieu that is encounter inside tumours and in endo/lysosomal vesicles upon cell uptake.