Peptide-coated gold nanoparticles can be used to activate or inhibit the growth of blood vessels. This is the new finding from a team of physicists and biologists at the University of Southampton in the UK. The researchers say that their experiments could be an important step towards developing better cancer therapies using coated nanoparticles.
Angiogenesis is the process by which new blood vessels form throughout the body. It is vital for growth and development and plays a major role in processes such as wound healing, rheumatoid disease and in pregnancy. However, it is also involved in tumour growth and metastasis; therefore, controlling angiogenesis could lead to new cancer therapies
Angiogenesis starts when specific molecules that bind to angiogenic receptors on cells activate endothelial cells, which line the interior of blood vessels. This activation leads to the endothelial cells proliferating – in a sort of cascade – and then assembling to form new vascular structures. The process is activated (via pro-angiogenic factors) by signals that regulate new vessel growth or inhibited (via anti-angiogenic ones).
Avoiding side effects
Although angiogenic drugs can be used to increase or reduce blood-capillary growth in certain diseases, most of these treatments are only effective for a short time. And more often than not, the drugs need to be administered in large quantities – something that can lead to side effects and even toxicity.
Physicist Antonios Kanaras, biologist Timothy Millar and colleagues believe that nanoparticles could solve some of the problems associated with administering angiogenic drugs. Nanoparticles are efficient drug-carrying and drug-delivery vehicles because they can encapsulate large quantities of therapeutic molecules. What is more, their surfaces can be covered with receptor molecules (usually antibodies). These can ensure that the drugs are delivered to specific parts of the body – targeting a tumour, for example.
The team looked at how three types of peptide-coated gold nanoparticles can activate or inhibit blood-vessel growth in vitro. The first peptide (which the researchers called P1) binds to the “vascular endothelial growth factor” receptor and promotes so-called signal-cascade activating genes; the third peptide (P3) binds to the neurophilin-1 receptor and blocks blood-capillary formation; and the second (P2) is a control because it does not interact with either of these receptors but simply enters cells.
Healing wounds
“We found that the ‘activating’ nanoparticles accelerate angiogenesis by a factor of two, while the ‘inhibiting’ ones significantly prevent angiogenesis,” Kanaras says. Stimulating angiogenesis can be useful in situations where vascular growth is desirable, such as in wound healing, but inhibiting angiogenesis will be important for slowing tumour growth, or stopping it altogether, he says.
Kanaras believes that such studies are critical for understanding how nanoparticles can affect blood-vessel growth and will open up new directions in angiogenic treatment using gold nanoparticles as a platform for drug development.
“Manipulating tumour angiogenesis is certainly the next big step in this research,” he claims. “It is well known that cancer cells need angiogenesis to grow. Will it really be possible for us to stop angiogenesis near a tumour site using functionalized nanoparticles? And how efficient could such a strategy be? These are the questions on which our research group is currently focusing.”
The experiments are described in ACS Nano.
