"One of the limitations of a receptor-based approach is that you just don't hit everything," Tsourkas said. "It's hard to recommend them as a screening tool when you know that the target receptors are only expressed in 30% of tumors."
"One of the reasons we like our approach is that it hits a lot of tumors; almost all tumors exhibit a change in the acidity of their microenvironment."
The Penn engineers took advantage of something known as the Warburg effect, a quirk of tumor metabolism, to get around the targeting problem. Most of the body's cells are aerobic; they primarily get their energy from oxygen. However, even when oxygen is plentiful, cancerous cells use an anaerobic process for their energy. Like overtaxed muscles, they turn glucose into lactic acid, but unlike normal muscles, tumors disrupt the blood flow around them and have a hard time clearing this acid away. This means that tumors almost always have a lower pH than surrounding healthy tissue.
Some imaging technologies, such as magnetic resonance spectroscopy, can also take advantage of tumors' low-pH microenvironments, but they require expensive specialized equipment that is not available in most clinical settings.
By using glycol chitosan a sugar-based polymer that reacts to acids the engineers allowed the nanocarriers to remain neutral when near healthy tissue, but to become ionized in low pH. The change in charge that occurs in the vicinity of acidic tumors causes the nanocarriers to be attracted to and retained at those sites.
This approach has another benefit: the more malignant a tumor is, the more it disrupts surrounding blood vessels and the more acidic
|Contact: Evan Lerner|
University of Pennsylvania