Nanoparticles for Pancreatic Cancer Therapy

Pancreatic ductal adenocarcinoma resists chemotherapy, and most polymeric nanocarriers persist in tissue because their backbones cannot be degraded. This project will develop nanoparticles that co-deliver a chemotherapeutic (gemcitabine or paclitaxel) with siRNA targeting chemoresistance pathways, addressing both barriers together. Carriers will be synthesised by PET-RAFT polymerisation, a visible-light living radical technique giving precise control over molecular weight and block architecture under mild aqueous conditions compatible with functional monomers.

Degradability will be built into the backbone by radical ring-opening copolymerisation of lipoate monomers, whose cyclic disulfides insert cleavable linkages responsive to the elevated glutathione levels in tumour cells; thionolactone and cyclic ketene acetal comonomers will be evaluated as alternatives. The candidate will correlate copolymer composition with nanoparticle stability, degradation rate and payload release, then assess knockdown and cytotoxicity in in-vitro, with potential for preclinical in vivo evaluation using cutting edge models. The project will be conducted in collaboration with Professor Craig Hawker (UCSB).