Parathan Ramamurthi, University of Sydney

Monday, 25 September 4:00pm – 5:00pm

This seminar will be delivered in Chemistry Lecture Theatre 4

Speaker: Parathan Ramamurthi, University of Sydney

Host: Dr Vien Huynh

Title: Molecular polymer bottlebrushes with tunable hydrophilic-hydrophobic character and their interaction with serum proteins, cancer cells and tumours

Abstract: The prospect of highly selective drug transport to tumour tissue has become ever more likely via nanoparticle drug carriers, which can confer enhanced pharmacokinetic properties compared to their small-molecule counterparts. These improvements however remain marginal in scope, given the complex nature of the tumour microenvironment which can hinder a nanoparticle’s performance, as well as protein corona formation around nanoparticles in complex biological environments. This necessitates careful adjustments of the chosen nanocarrier’s physicochemical characteristics to circumvent these physiological barriers and attain sufficient accumulation levels within the tumour. Although most physicochemical parameters such as nanoparticle size, shape and surface charge/chemistry have been extensively investigated as drivers of nanoparticle behaviour in vivo, the hydrophilic-hydrophobic balance has remained mostly unexplored in the same regard. The first part of this talk addresses this parameter’s influence on a nanoparticle’s efficiency in tumour penetration, using a library of molecular polymer bottlebrushes (MPBs) with systematically varied amphiphilicity levels. Although in vitro cancer models showed a negligible effect of nanoparticle hydrophobicity, the effects of adjusting this parameter were more pronounced in tumour-bearing mice, wherein biodistribution, initial tumour uptake and prolonged tumour retention was favoured by MPBs bearing intermediate hydrophobicity levels.

Motivated by the improved tumour-homing performance of the intermediately hydrophobic MPBs in vivo, the second part of this talk details the investigation into the potential amphiphilicity-dependence of these MPBs adsorption of serum proteins and interactions with cellular membranes. Although the results demonstrated that MPB hydrophobicity had a meagre effect on the particle’s affinity for albumin chosen as a model protein, the presence of serum proteins had a significant outcome on the MPBs’ association with cancer cells, although little difference was observed based on each particle’s hydrophobicity. The effects of hydrophobicity were however felt upon incubation with biomimetic cell membranes, in which membrane perturbations were more easily induced by the more hydrophilic MPBs.