Nanoparticles advance photodynamic therapy to kill tumor cells

Photodynamic therapy (PDT) is a powerful approach for destroying tumors, one that uses light and a light-sensitive chemical to rapidly kill cells.

Unfortunately, PDT is associated with significant side effects that largely result from the fact that light-sensitive chemicals, or photosensitizers, distribute themselves throughout the body and thus can damage healthy as well as malignant cells. Another limitation arises because the frequency of light needed to excite the photosensitizers can only pass through a few millimeters of skin.

To reduce or even eliminate PDT’s therapy-limiting side effects, researchers are attempting to increase uptake of photosensitizers by tumors and decrease uptake by healthy cells, and to do that investigators are relying heavily on nanoparticles. In a new report, investigators at the State University of New York in Buffalo describe a novel nanoparticle that encapsulates a photosensitizer and a special dye molecule that can absorb light capable of traveling deep into the body and transfer that light energy to the photosensitizer. Tests with cultured cancer cells show that this nanoparticle kills tumor cells.

Paras Prasad, Ph.D., principal investigator of the Multifunctional Nanoparticles in Diagnosis and Therapy of Pancreatic Cancer program, one of National Cancer Institute-funded Cancer Nanotechnology Platform Partnerships, led this research effort. The results of this work appear in the Journal of the American Chemical Society.

The main component of this new system is an organically modified silica nanoparticle that Prasad’s group has been developing for several years. Within this nanoparticle, the investigators encapsulated a novel dye molecule that can absorb and emit light in spite of being packed closely to other dye molecules; the optical performance of most dye molecules drops precipitously when they are in close contact with other dye molecules. The nanoparticles also contain a photosensitizer that efficiently absorbs light emitted by this particular dye. This photosensitizer, known as HPPH, recently began to be tested in human clinical trials.

Initial tests with this nanoparticle formulation showed that it generated cell-killing reactive oxygen when irradiated with near-infrared light, the portion of the light spectrum that passes through skin and other tissues easily. Additional experiments showed that tumor cells took in these nanoparticles over a 3-hour period and that when the cells were subsequently irradiated with near-infrared light, the cells died from the internally generated reactive oxygen.

In a second study, published in the journal Molecular Pharmaceutics, the investigators showed that nanocrystals of HPPH could also trigger reactive oxygen production in tumor cells. The purpose of this study was to determine if it was possible to create a formulation of HPPH that is stable in water yet retains its cell-killing activity. HPPH belongs to a category of drugs, which includes many anticancer agents, that are poorly soluble in water. Pure drug nanocrystals dispersed readily in water and were taken up by tumor cells.

This work, which was supported by the National Cancer Institute’s Alliance for Nanotechnology in Cancer, is detailed in two papers. Both papers were published online in advance of print publication. An abstract of the paper titled, “Organically modified silica nanoparticles co-encapsulating photosensitizing drug and aggregation-enhanced two-photon absorbing fluorescent dye aggregates for two-photon photodynamic therapy,” is available at the journal’s website. View abstract.

An abstract of the paper titled, “New method for delivering a hydrophobic drug for photodynamic therapy using pure nanocrystal form of the drug,” is available at the journal’s website. View abstract.