UCLA scientists have unlocked an important mechanism that allows chemotherapy-carrying nanoparticles—extremely small objects between 1 and 100 nanometers (a billionth of a meter)—to directly access pancreatic cancer tumors, thereby improving the ability to kill cancer cells and hence leading to more effective treatment outcome of the disease. The researchers also confirmed the key role of a peptide (an extremely small protein) in regulating vascular access of the nanoparticle to the cancer site.
The discovery is the result of a two-year study co-led by Drs. Huan Meng and André Nel, members of UCLA‘s Jonsson Comprehensive Cancer Center and the UCLA California NanoSystems Institute. The findings are important as they demonstrate how the delivery of chemotherapy to pancreatic cancer can be improved significantly through the use of smart-designed nanoparticle features.
Pancreatic ductal adenocarcinoma is generally a fatal disease, with a five-year survival rate of less than 6 percent. The introduction of nanocarriers as delivery vehicles for common chemotherapy agents such as the drug irinotecan, has led to improved survival of patients with this disease. However, the reality is that nanocarriers may not always reach their intended target in sufficient numbers because of a constraint on their ability to transit through the blood vessel wall at the tumor site, leading the encapsulated drugs to be diverted or lost before they can deliver their payload.
A key challenge for scientists is how to help nanoparticles travel to and be retained at tumor sites. This can be accomplished by custom-designed or engineered nanoparticles that overcome common challenges, such as the presence of a dense tissue surrounding the pancreas cancer cells. Prior research has identified a major vascular access mechanism that relies on a vesicle transport system, which can be turned with a peptide called iRGD in the blood vessel wall. iRGD is therefore potentially useful to optimize the delivery of cancer drugs by the nanoparticle to the tumor.
The UCLA research team designed a nanoparticle comprised of a hollow silica core surrounded by a lipid bilayer to enhance the delivery of irinotecan in an animal model with pancreatic cancer. The invention is called a silicasome. The researchers proposed that the therapeutic benefit of the irinotecan containing nanoparticles may be enhanced when combined with the injection of iRGD. The investigators used the nanoparticle plus the iRGD to deliver irinotecan in a robust animal model for pancreatic cancer that closely mimics human disease.
The study is published online in the Journal of Clinical Investigation.