Plasma polymer based metal affinity coatings for ELISA
Anthracyclines such as doxorubicin are among the most effective chemotherapy agents for the treatment of a wide variety of cancer types. Although many mechanisms of action have been proposed, it is broadly accepted that the primary mechanism of action in cancer cells involves DNA damage. However, doxorubicin also attaches covalently to DNA in a reaction that is mediated by formaldehyde.
The research team has demonstrated that the delivery of formaldehyde via suitably designed pro-drugs greatly enhances the rate of cell death. This raises the possibility that efficient and specific delivery of pro-drug to cancer cells, for example using a nanoparticle delivery system, might allow lower doses of doxorubicin to be administered. This in turn has the potential reduce the incidence of cardiotoxicity associated with doxorubicin use and extend patients’ lives.
A class of size controlled liposomal nanoparticles has been designed which allow the delivery of either doxorubicin or pro-drug to target cells. Excellent preliminary results have been achieved in vitro with high efficacy demonstrated and low toxicity to cells.
We are developing an extended panel of nanoparticle compositions and structures using the CSIRO RAMP high throughput molecular fabrication capability and screening these for behaviour against multiple cell lines and in multiple treatment regimes.
The systems are being characterised using molecular and biomolecular imaging and analytical approaches including confocal microscopy, ToF-SIMS, XPS and AFM. These studies will be supported by multivariate analysis including principal components analysis, cluster analysis and self organising maps.
This is a CSIRO-LIMS joint project.