PHOTODYNAMIC THERAPY/CANCER TREATMENT: Inside and outside: New approach to PDT doubles toxicity for cancer cells
Most photodynamic therapy (PDT) operates using individual molecules that, when heated with light, destroy diseased tissue. But a new approach developed by researchers in the University of Hull’s (Hull, England) department of chemistry uses nanoparticles that can each deliver hundreds of molecules to a cancerous tumor.1
A variety of light-sensitive molecules (photosensitizers) are commonly used in PDT to produce toxic reactive oxygen species; each type of molecule absorbs a specific range of light. The Hull researchers found that they were able to realize far more reactive oxygen species using the same amount of light when they placed one type of photosensitizer inside each nanoparticle and applied a different type to the outside of the particle.
But that's not the only secret to the team's success. According to lead researcher Ross Boyle, the specific size of the nanoparticles (mean sizes were 45 ± 10 nm and 95 ± 10 nm, respectively)—and their shape—facilitates penetration of tumors. "Our nanoparticles have been designed so the pressure in the blood vessels will push them through the space between the cells to get into the tumor tissue," says Boyle.
The nanoparticles are made from polyacrylamide, which limits the leaching of its contents while in the bloodstream. When activated with light, however, the toxic reactive oxygen species produced can diffuse freely out of the particles; so damage is confined to the targeted area.
In the researchers' experiments, uptake of the nanoparticles by human Caucasian colon adenocarcinoma cells (HT29) was determined by flow cytometry and confocal microscopy. While the nanoparticles were able to penetrate the cancer cells, the researchers also found that they could be effective when near—not just when inside—the cells. “Some types of cancer cell are able to expel conventional drugs, so if we can make this kind of therapy work simply by getting the nanoparticles between the cancer cells, rather than inside them, it could be very beneficial,” says Boyle. —Barbara G. Goode
1. M. Kuruppuarachchi et al., Mol. Pharm. 8 (3), 920–931 (2011).