Mesoporous silica (mSiO2) can be used to carry anti-cancer drugs to tumour sites in mice. So say researchers at the University of Wisconsin−Madison in the US who have succeeded in making TRC105-conjugated mSiO2 labelled with radioactive copper for the first time. TRC105 is a chimeric monoclonal antibody that binds to both human and mouse endoglin, or CD105 (a type I membrane glycoprotein found on endothelial cell surfaces).
mSiO2 nanoparticles are a promising new category of drug delivery vehicle because they are biocompatible and non-toxic. Their surfaces can also be easily modified and their mesopores (which are around 2–3 nm across) can hold a significant amount of therapeutic molecules.
Researchers have tried conjugating various targeting ligands (such as folic acid, transferrin, aptamer and herceptin) to mSiO2 nanoparticles for in vitro or in vivo tumour cell targeting, with limited success. A team led by Weibo Cai has now taken an important step forward in this field by developing TRC105-conjugated and 64Cu-labelled mSiO2 (or 64Cu-NOTA-mSiO2 -PEG-TRC105). Copper-64 (which has a half-life of 12.7 h) is commonly employed as an isotope in positron emitting tomography (PET) imaging and NOTA is a well-known chelator for 64Cu labelling.
Successful anti-cancer drug delivery
In vivo tumour targeting experiments by Cai and colleagues clearly show that the 64Cu-NOTA-mSiO2-PEG-TRC105 accumulates at mouse breast tumour sites (known as "4T1") thanks to TRC105-mediated binding to CD105 in tumour blood vessels. As a proof of concept, they also demonstrated that they could successfully deliver the anti-cancer drug doxorubicin (DOX) in mice with 4T1 tumours by injecting DOX-loaded 64Cu-NOTA-mSiO2-PEG-TRC105 into the animals.
Cai, together with team members Feng Chen and Hao Hong, synthesized mSiO2 nanoparticles around 80 nm in size using a well-established soft-template method. They then conjugated the mSiO2 to TRC105 and NOTA through polyethylene glycol (PEG) linkers. The ensemble was labelled with 64Cu to form the 64Cu-NOTA-mSiO2-PEG-TRC105 nanoconjugate.
The team says that it is now busy trying to find ways to further enhance the amount of drug carried by the nanoconjugates and improving in vivo targeting efficiency of functionalized mSiO2. "The next stage in our experiments is to show that our nanoparticles can be employed in in vivo image-guided cancer therapy," Cai told nanotechweb.org.
"Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is essential for tumours to grow and progress," he added, "and targeting tumour vasculature is a much more efficient strategy than targeting tumour cells themselves. CD105 is an ideal marker for tumour angiogenesis because it is almost exclusively expressed on proliferating endothelial cells. We are the only group in the world actively working on imaging/targeting of CD105."
