Drug-Delivery Breakthrough Relies on Nanoparticles to Starve Pancreatic Cancer Cells

Pancreatic cancer is one of the most dangerous and intractable of all cancers. But now, a team of researchers at Massachusetts General Hospital (Boston) under Tayyaba Hasan, a professor of dermatology at Harvard Medical School, has developed two nanoparticles that can deliver two or more drugs simultaneously, shrinking pancreatic cancer tumors and reducing their spread. Hasan and two research fellows in her lab, Prakash Rai and Lei Z. Zheng, presented their initial results on November 17 at the International Conference on Molecular Targets and Cancer Therapeutics, held by the American Association for Cancer Research (Philadelphia), the National Cancer Institute (Bethesda, MD), and the European Organisation for Research and Treatment of Cancer (Brussels).As reported in Technology Review, published by the Massachusetts Institute of Technology (Cambridge, MA), the team's "nanocells" combine light-based therapy with molecules that inhibit the growth of cancer cells or of the blood vessels that feed them. Consisting of solid polymer nanoparticles, the first type of nanocell houses a photosensitive drug called verteporfin, which creates toxic oxygen radicals when exposed to specific wavelengths of light, effectively starving tumors by cutting off their blood supply. These nanoparticles are encapsulated in lipid particles along with bevacizumab, an antibody that specifically inhibits the growth of new blood vessels by blocking a protein called VEGF.When the nanocells are injected intravenously, they deliver both drugs directly to the inside of cancer cells. While blood vessels in normal tissue are impermeable to the nanoparticles, blood vessels in tumors have much larger pores, enabling the nanoparticles to pass through. As a result, the nanoparticles accumulate inside the tumors and deliver more of their payload to the cancer cells than to healthy cells.To test their discovery, the team implanted human pancreatic cancer cells in mice and allowed tumors to grow. They then injected the mice with a single dose of the nanocells and exposed the tumors to long-wavelength light. The tumors in mice treated with both drugs together via the nanocell vehicle shrank more than those in mice treated with either drug alone. The mice treated with the nanocells also had at least two times fewer metastases to the liver, lungs, and lymph nodes."Injecting these things as separate entities is not as effective as combining them into one construct," Hasan remarks. She hypothesizes that this is the case because the nanocells fuse with the tumor cells and deliver the bevacizumab inside the cell rather than merely to the outside.Hasan hopes that both nanocells will be tested in pancreatic cancer patients within a few years. Because bevacizumab and verteporfin are already FDA approved, she believes that the team's nanocells designed for use with these drugs will likely be the first ones tested.For more details, see the Technology Review article "Big Hope for Tiny Particles."