Poster Presentation 2nd Australian Cancer and Metabolism Meeting 2017

Exploiting tumour acidity for polymer based drug delivery (#41)

Elizabeth G Whitty 1 2 3 , Erin R Andrew 1 , Aude M Fahrer 1 , Patrice Castignolles 2 , Marianne Gaborieau 3 , Richard Callaghan 1
  1. Department of Biomedical Science and Biochemistry, Research School of Biology, College of Medicine, Biology and Environment , The Australian National University, Canberra, ACT, Australia
  2. Australian Centre for Research on Separation Science (ACROSS), School of Health and Science, Western Sydney University, Parramatta, NSW, Australia
  3. Molecular Medicine Research Group, School of Science and Health, Western Sydney University, Parramatta, NSW, Australia

An acidic micro-environment is a hallmark feature of solid tumours generated by metabolic adaptations including an increased reliance on glycolysis and its concomitant production of lactic acid. The acidic environment has deleterious effects on many anticancer drugs; however, several novel therapeutic strategies are beginning to exploit this property. Our consortium has recently developed three configurations of poly(sodium acrylate) (PNaA) as a pH-sensitive drug delivery system. Initial efforts are focussing on the anticancer drug cisplatin, which is beset with poor stability, toxicity and pharmacokinetic properties. Loading cisplatin onto a polymer will circumvent many of these issues by providing targeted delivery and increased stability. PNaA is avidly loaded with the anticancer drug cisplatin at pH9 and the attachment is stable, fully reversible and displays a highly pH-dependent release process. The three configurations of PNaA differ in their branching structure and thereby offer distinct loading capacities. In the present investigation we have undertaken preliminary characterisation of PNaA in a simple monolayer cell culture system. The initial objective was to assess whether the unloaded polymer classes displayed any inherent toxicity to cancer cells. None of the polymer classes caused significant alterations in cell cycle progression nor were they associated with marked apoptosis. The second objective compared the growth inhibitory effects and potency of cisplatin loaded polymer with administration of drug alone. The potency of PNaA-delivered cisplatin was greater than observed with drug alone and demonstrates the viability of this polymer as a delivery system. The subsequent phase of investigation will assess the efficacy of PNaA as a cisplatin delivery system in solid tumour models.