8 Jun 2018

Monash scientists in nanomedicine advance

Ms Shweta Jagdale and Associate Professor Christoph Hagemeyer
in the lab.
by Anne Crawford

The emerging field of nanomedicine holds great potential for biomedical discovery and for new forms of treatment for diseases such as heart conditions and cancer. Nanoparticles can fly under the radar of the immune system, which would otherwise identify them as foreign and destroy them, to reach their intended target. They can be used, for example, to efficiently transport a drug to the specific site of disease.

But because the field is so young the possible side-effects of sending these tiny structures into the human body are still unknown.


A team at Monash University’s Australian Centre for Blood Diseases (ACBD) led by Associate Professor Christoph Hagemeyer has developed a possible solution to one emerging problem in the brave new world of nanomedicine: the build-up of non-degradable nanoparticles in the body.

Associate Professor Hagemeyer said the research, published yesterday in ACS Nano, was prompted by increasing concerns about using artificial polymers because the body cannot degrade them. Previous research had shown that the plastic-like particles formed deposits in the kidneys of mice repeatedly exposed to them, he said.

The researchers developed what they have called ‘PASKE’, a combination of naturally occurring amino acids that are biodegradable yet share the benefits of the FDA-approved polymer PEG or poly(ethylene glycol). PEG is commonly used in the pharmaceutical industry including to enhance the action of insulin in diabetes, but does not appear to break down in the body, Associate Professor Hagemeyer said.

“We showed that PASKE particles fly under the radar of the immune system and circulate in the blood for an extended period of time. More importantly, once they enter the tissue our protein particles were completely gone after 24 hours,” he said. “The cells in the body had the ability to digest the particle and basically recycle and re-use the amino acids they are made from.”

The researchers demonstrated that PASKE particles have potential as a molecular imaging tool for thrombosis and could “act as a versatile platform for superior nanomedicine”.

“The main advantage of nanomedicine is that nanoparticles can load a lot of drug and deliver it to the tissue of interest rather than distributing it throughout the body quite randomly as with current treatments,” Associate Professor Hagemeyer said. “So you can reduce the off-target or side effects.

“This is the one of the first reports in which tailored protein particles have been used as a true alternative to classic polymers.

“One of the other advantages of our platform is that you can design it very precisely by changing the amino acid sequence.”

This could mean that treatments could be personalised better by loading several different molecules in the particle specifically suited to the individual patient’s disease.

The research is a collaboration between the ACBD and University of Melbourne scientists led by world-renowned material scientist Professor Frank Caruso. The first author was Dr Thomas Bonnard who received funding from the People Programme (Marie Curie Actions) of the European Union to conduct this work in Australia. The work was also supported by the National Health and Medical Research Council, and Australian Research Council.

The researchers, who are now refining the PASKE nanoplatform further, are seeking international and local investors to develop it commercially.

Reference
Bonnard, Thomas; Jayapadman, Anand; Putri, Jasmine; Cui, Jiwei; Ju, Yi; Carmichael, Catherine; Angelovich, Thomas; Cody, Stephen; French, Shauna; Pascaud, Karline; Pearce, Hannah; Jagdale, Shweta; Caruso, Frank; Hagemeyer, Christoph. Low Fouling and Biodegradable Protein-Based Particles for Thrombus Imaging. ACS Nano Article ASAP DOI: 10.1021/acsnano.8b02588

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