Metal-enhanced fluorescence could aid photodynamic therapy

Lynn M. Savage

Photodynamic therapy uses light-activated chemicals to treat diseases such as cancer and age-related macular degeneration, but the technique can be difficult to control precisely. The chemicals — drugs called photosensitizers — are injected into a patient and are taken up by diseased cells. The key to treatment is that, when light illuminates the photosensitizer, singlet oxygen is generated. A highly reactive form of oxygen, ¹O₂ is highly cytotoxic — damaging or destroying the tumor or other cells in close proximity.

Unfortunately, creating too little ¹O₂ results in ineffective treatment; too much increases the likelihood that healthy cells surrounding a tumor, for example, also will be affected. Adjusting the light intensity can help but is tricky because high intensity can lead to photobleaching of the sensitizer, and low intensities can increase exposure time and the risk of vascular shutdown.

A solution of the photosensitizer Rose Bengal (RB) and a reagent (GR) that senses singlet oxygen exhibits enhanced fluorescence intensity when brought into contact with silver island film (SiF). Reprinted with permission of PNAS.

Now, however, a group of researchers from the University of Maryland Biotechnology Institute in Baltimore has developed a technique that uses metal nanoparticles to provide a higher degree of control over the amount of ¹O₂ that is created during exposure to light of constant intensity.

Led by Yongxia Zhang of Chris D. Geddes’ fluorescence group at the institute, the investigators placed a solution comprising the photosensitizer Rose Bengal and green reagent, a selective sensor for ¹O₂, on glass substrates dotted with islands made of silver film. The reagent and the photosensitizer have fluorescence peaks of 525 and 588 nm, respectively.

When irradiated with UV light from a 100-W mercury lamp for 2 min, the fluorescence emission intensity of the green reagent that was located over the silver islands increased by about 3.3 times compared with that of the reagent over uncoated glass. The researchers used a fiber optic spectrometer made by Ocean Optics Inc. of Dunedin, Fla., to measure the fluorescence emissions.

As they report in the Feb. 12, 2008, issue of PNAS, the increased emission intensity is a function of the increased absorption cross section of the photosensitizer — in essence, the probe absorbed significantly more light. The group has tested the system using various photosensitizers and different thicknesses of silver islands, which has led to consistent findings. The investigators extrapolate that converting the silver islands into silver-coated nanoscale particles will enable them to bring the process to the cellular level, thereby enhancing photodynamic therapy through precise control of ¹O₂ production.