While targeting nanoparticles to attack cancer cells can be effective at reducing primary tumors, they tend to create tiny holes within blood vessel walls that let some cancer cells escape and metastasize elsewhere. This is a serious side effect that may limit the usefulness of many nanoparticle-based cancer therapies in the long run, so researchers at National University of Singapore have been studying this matter and how to address it.
The team identified that nanomaterial-induced endothelial leakiness is caused by a variety of nanoparticles, including those made from silica, gold, and titanium dioxide. Moreover, animal experiments demonstrated that the pores the particles make within blood vessels allow for breast cancer cells to pass through and start new tumors.
The researchers also noted that a protein called Angiopoeitin-1 can be made to close the vessel pores that nanoparticles produce and lower the incidence of metastasis associated with nanoparticle therapy. It does this by acting on TIE2, a cell surface regulator in blood vessels that makes them contract and block openings.
“The study showed that Angiopoeitin-1 could potentially be used as a counter mechanism to limit and reverse the leakiness induced by nanoparticles,” said Professor HO Han Kiat from the Department of Pharmacy at National University of Singapore, one of the study leads. “This helps to decrease the extravasation and transportation of cancer cells to other tissues in cancer patients.”
Study in Nature Nanotechnology: Nanoparticles promote in vivo breast cancer cell intravasation and extravasation by inducing endothelial leakiness