Members of the camelid family have particular heavy-chain antibodies in their blood known as nanobodies that may serve as therapeutic proteins. One of the most powerful advantages of nanobodies is that they can be easily attached to other proteins and nanoparticles by simple chemical procedures.
Scientists at the Department of Pharmaceutics and Analytical Chemistry, University of Copenhagen, have designed nanoparticle systems of smaller than 150nm that are decorated with nanobodies expressing high specificity for the cancer marker Mucin-1, which is connected to breast and colon cancer.
"This is a very effective and a highly promising approach in experimental cancer gene therapy, while minimising adverse-related reactions to cancer nanomedicines. Futhermore the research supports our aim for rational design and engineering of effective and safer nanomedicines for the future. We have taken the first step, but of course more work is needed to support the efficacy of this system for cancer treatment,” says Professor Moein Moghimi, who heads the Centre for Pharmaceutical Nanotechnology and Nanotoxicology at University of Copenhagen.
Compared to other protein-based drugs, nanobodies are very small. They are ten times smaller than intact antibodies. They are also less sensitive to temperature and pH changes and can be easily linked to nanoparticles and other proteins. These properties make nanobodies very interesting for targeting of cancer cells.
The article in the Journal of Controlled Release describes how a Mucin-1 nanobody was linked to specialised nanoparticles made from polymers carrying a killer gene known at truncated-Bid. When expressed, the gene product triggers cells to commit suicide.
However, the expression of the killer gene was under the control of the cancer-specific Mucin-1 promoter as to avoid non-specific cell killing. These procedures are also referred to as “transcriptional targeting”, which can prevent normal tissue toxicities associated with other cancer treatments. Indeed, the formulation proved to be highly effective in killing cancer cells expressing the Mucin-1 marker, while no harm was done to the normal cells or cancer cells that did not express the Mucin-1 marker.
The efficacy of these nanoparticles is now being tested in animal models. Another development is that the team has now purified a second and a highly effective nanobody against another cancer marker (Her-2) expressed by certain breast tumors.
Citation: Elham Sadeqzadeh, Fatemeh Rahbarizadeh, Davoud Ahmadvand, Mohammad J. Rasaee, Ladan Parhamifar and S. Moein Moghimi, 'Combined MUC1-specific nanobody-tagged PEG-polyethylenimine polyplex targeting and transcriptional targeting of tBid transgene for directed killing of MUC1 over-expressing tumour cells', Journal of Controlled Release doi:10.1016/j.jconrel.2011.06.022
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