Stephen M Mahler
Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Australia
Title: Antibody-targeted delivery of nanoparticles utilizing bispecific antibodies for applications in oncology
Biography
Biography: Stephen M Mahler
Abstract
Incorporating drugs such as small molecules, siRNA and proteins into nanoparticles seeks to achieve greater therapeutic efficacy and reduced systemic toxicity. However, despite extensive research into nanomedicine, there are few approved, passively-targeted products approved for use including liposomal nanoparticles Myocet, Doxil, Daunoxome and Depocyt, Abraxane (albumin-based nanoparticle) and Genexol-PM (micelle).
There are a number of barriers to successful nanoparticle-mediated drug delivery, including the reticular endothelial system, efficient extravasation, crossing the anatomical and physical barriers between endothelial and tumour cells, penetrating the tumour structure, endocytosis uptake and intracellular release of therapeutic agents. Active targeting of nanoparticles using antibodies or peptides can improve nanoparticle delivery by enhancing uptake into targeted tumour cells. While targeting has little or no impact on systemic delivery challenges, actively-targeted nanoparticles offer the advantage of having increased tumour cell uptake through receptor-mediated endocytosis, compared to passively-targeted nanoparticles.
We are investigating a range of different strategies to empower nanoparticles with targeting antibody fragments that are highly specific to tumour cell receptor targets such as epidermal growth factor receptor (EGFR) and other tumour-associated targets. The targeting of nanoparticles through the use of bispecific antibodies is described.