FEATURES & INNOVATIONS
Nanomedicine
breakthrough hailed as ‘world changing’
A nanoparticle designed by researchers at the A*STAR Institute of Bioengineering and Nanotechnology and the IBM Almaden Research Center that could help combat superbugs garners international acclaim.
T
he quest to develop novel meth- ods to combat drug-resistant and infectious diseases
such
as Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), which continue to pose serious challenges to human health worldwide due to the inherent ability of the disease-causing microbes to develop antibiotic resistance, has been spurring innovative research into the medical applications of nanotechnology in recent years.
One of the most remarkable achieve- ments in the rapidly growing field of nanomedicine
has been the success-
ful synthesis of the first biodegradable polymer-based nanoparticle capable of combating multidrug-resistant microbes, which works by selectively targeting and tearing down bacterial cell walls and membranes1
. Designed by researchers at
the A*STAR Institute of Bioengineer- ing and Nanotechnology (IBN) and the IBM Almaden
Research Center, the
unique nanoparticle has been featured as one of Scientific American’s top ten world changing ideas. Referring to the novel design as a
‘nanotech knife’, as a way of describ- ing the lethally effective, precise nature of
the technology, Scientific American
has featured the work conducted by the team of A*STAR and IBM researchers in its special end-of-year report, ‘World Changing Ideas — 10 New Technologies Tat Will Make a Difference’ published in its December 2011 issue. “We are delighted that Scientific Ameri- can recognizes our nanoparticle discovery
as a world changing idea,” says Jackie Y. Ying, IBN’s executive director. “Tis is an excellent affirmation of our nanotech- nology research against drug-resistant bacteria and we will now be focusing on developing these nanoparticles for clinical and consumer applications.”
A new way to fight disease Antibiotics
traditionally work which on the
principle of using chemical compounds to act on specific molecular targets within bacteria,
leads to therapeutic
specificity but allows resistance develop- ment through mutation. In contrast, the bacteria-killing
nanoparticle developed
by the IBN research team and colleagues at IBM may help to circumvent many of the problems associated with con- ventional methods of antibiotic therapy by utterly disintegrating the bacteria’s physical structure at the outset. Tis novel methodology has therefore been garner- ing widespread interest due to the way in which it offers a fundamentally different approach to fighting disease. Te nanoparticles begin their assault
on harmful bacteria by forming cat- ionic (positively charged) clusters that are drawn towards the anionic (negatively charged) bacterial cell membranes. By selectively binding to the bacte- cell membranes in this way, the
rial
nanoparticles avoid harming human cell membranes, cells, ing,
leaving red blood
for example, intact. After target- puncturing and destabilizing
the
bacterial cell wall, the nanoparticles eventually break down and kill the bac- terial cell. Te physical destruction of
A*STAR RESEARCH OCTOBER 2011–MARCH 2012
The research team (from left to right): Dr Chuan Yang, IBN Research Scientist, Dr Shujun Gao, IBN Research Officer, Dr Yiyan Yang, IBN Group Leader, Dr James L. Hedrick (IBM Almaden Research Center), and Dr Jeremy Tan, IBN Research Scientist
the bacterial cell membrane can delay or eliminate resistance development. Using transmission electron micros-
copy, the IBN research team led by Yiyan Yang observed the extent of damage inflicted by the nanoparticles on the bacterial cell walls and membranes, and was thus able to confirm that selective cell lysis had been achieved. “We hypothesize that the cationic nanoparticles could interact easily with the negatively charged cell wall by means of an electrostatic interaction, and the steric hindrance imposed by the mass of nanoparticles in the cell wall and the hydrogen-binding/electrostatic interac- tion between the cationic nanoparticle and the cell wall may inhibit cell wall syn- thesis and/or damage the cell wall, result- ing in cell lysis,” says Yang. “In addition, the nanoparticles may destabilize the cell membrane as a result of electroporation and/or the sinking raft model, leading to cell death. Te nanoparticles damaged the cell wall and cell membrane like a ‘knife’.” Te team discovered that the nanopar-
ticles could efficiently kill Gram-positive bacteria, MRSA and fungi, even at low concentrations. Te nanoparticles showed no significant activity against red blood cells, and no obvious acute toxicity was observed during in vivo studies in mice, even at concentrations well above their effective dose. Te nanoparticles themselves are easily
broken down by enzymes in the human body as they are composed of biodegrad- able polymers. Whereas most antimicro- bial polymers developed to date have been non-biodegradable,
which render dif- ficulty in obtaining regulatory approval, 91
© 2011 IBN
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