Given that cancer is a disease caused by gene mutations, cancer researchers have been striving to develop gene therapies aimed at correcting these mutations. However, these efforts have been hobbled by the difficulty in safely and efficiently delivering anticancer genes to tumors. Nanoparticles, however, may solve these delivery issues, and two recently published studies, using two different types of nanoparticles, lend credence to that hypothesis.
Miqin Zhang, Ph.D., PI of the Nanotechnology Platform for Pediatric Brain Cancer Imaging and Therapy project at the University of Washington in Seattle, led a group of researchers that developed a targeted polymer nanoparticle that efficiently delivered a model gene into two types of cancer cells. More importantly, the gene functions properly once it enters the targeted cells. In the second study, Mansoor Amiji, Ph.D., PI of the Nanotherapeutic Strategy for Multidrug Resistant Tumors Platform Partnership at Northeastern University, and doctoral student Padmaja Magadala, M.S., used gelatin-based nanoparticles and a different targeting agent to efficiently deliver the same model gene to human pancreatic tumor cells. As in the first study, the delivered gene functioned properly inside the tumor cells.
The nanoparticle developed by Dr. Zhang's group was made of two polymers-polyethyleneimine (PEI) and polyethylene glycol (PEG)-linked to chlorotoxin, a small protein isolated from scorpion venom. Previous research by several research teams had shown that chlorotoxin binds many types of tumors, including gliomas and medulloblastomas, two types of brain cancer. PEI forms stable nanoparticles that bind deoxyribonucleic acid (DNA), but the resulting nanoparticles can be toxic. Adding PEG to the nanoparticles provides a biocompatible surface that greatly reduces the toxicity of PEI.
As a test, Dr. Zhang and her colleagues used these nanoparticles to deliver DNA that codes for green fluorescent protein (GFP), which is used widely to study gene expression. When added to tumor cells expressing the chlorotoxin receptor, the nanoparticles were quickly taken up by the cells. The cells also turned green, thanks to the expression of GFP. In contrast, nanoparticles lacking chlorotoxin were not taken up by the cells, and tumor cells lacking the chlorotoxin receptor did not take up the nanoparticles.
(The three scientists credited with discovering and developing GFP as a critical research tool were awarded the 2008 Nobel Prize in Chemistry. One of those scientists, Roger Tsien, Ph.D., is an investigator at NCI's Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer at the University of California, San Diego.)