Sep 6, 2013
'Living' PEGylation could improve cancer therapy
Researchers at the University of Michigan and IMRA America, Inc. in Ann Arbor have demonstrated that cancer cells can be made to take up increased amounts of therapeutic gold nanoparticles (AuNPs) using a new technique that they have dubbed "living" PEGylation. This technique allows to control the density and composition of functional ligands conjugated once or sequentially to the AuNP surface using heterobifunctional thiol-terminated poly(ethylene glycol) (HS-PEG-R).
Using "living" PEGylation the team, led by Duxin Sun, conjugated the modal targeting peptide RGD (HS-PEG-RGD) at different densities to AuNPs that were 20 nm in size. The researchers compared AuNP uptake in target U87-MG glioblastoma cells and non-target (MCF-7) cells using inductively coupled plasma optical emission spectrometry.
The experiments reveal that the targeting ligand/AuNP ratio (50/1) is critical to balancing AuNP specific uptake by cancer cells, and non-specific uptake by non-target cells, while minimizing uptake by macrophage cells.
The researchers also sequentially conjugated HS-PEG-COOH and HS-PEG-NH2 to the gold nanoparticles at different densities to develop double-charged AuNPs. Macrophage cells take up fewer of these nanoparticles compared to single-charged or non-charged AuNPs, an affect that is perpetuated as the overall charge of double-charged AuNPs becomes more neutral.
Applying "living" PEGylation to precisely control gold nanoparticle functionalization for cancer therapy can enhance nanoparticle targeting to cancer cells, reduce side effects from uptake by non-target cells, and minimize recognition by immune cells. We believe that such findings merit further in vivo studies of AuNPs containing an optimal density of a charged targeting ligand and a releasable, oppositely charged drug.
More information can be found in the journal Nanotechnology 24 355101.
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About the author
Dr Hongwei Chen is an assistant research scientist at the University of Michigan. His latest research focuses on theranostic nanoparticles for tumour imaging and therapy. He received his PhD in Polymer Science and Engineering in 2005 from The University of Science and Technology in China (USTC), and was a postdoctoral research fellow at USTC (2005–2007), Emory University (2008–2011), and the University of Michigan (2011-2012). Mrs Hayley Paholak is a PhD Candidate in Pharmaceutical Sciences at Michigan in Dr Duxin Sun’s lab, where she is developing nanoparticles to target, detect, and eradicate breast cancer stem cells. She received a Master’s degree in Pharmaceutical Engineering in 2011 from Michigan.