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UB scientists develop non-release nanoparticle to deliver photodynamic cancer therapy
By ELLEN GOLDBAUM
Contributing Editor
Scientists at UB's Institute for Lasers, Photonics and Biophotonics, working with colleagues at the Roswell Park Cancer Institute (RPCI), have developed a non-release, nanoparticle drug delivery system for photodynamic cancer therapy.
Confocal fluorescence image of tumor cells treated with HPPH-doped nanoparticles developed at UB.
According to the researchers, because the ceramic-based nanoparticle developed at the university never releases photosensitizing drug into the bloodstream, it could overcome the main side effect associated with photodynamic cancer therapy (PDT): the patient's strong sensitivity to light for four to six weeks after treatment.
The research was published online earlier this month in the Journal of the American Chemical Society.
A provisional patent has been filed.
PDT, which originated at RPCI, is one of the most promising treatments for cancer, and also is being investigated as a treatment method for cardiovascular, dermatological and ophthalmic diseases. PDT exploits the propensity of tumors to retain higher concentrations of photosensitive drugs than normal tissues.
When exposed to laser light, these drugs generate toxic molecules that destroy the cancer cells.
"What happens after treatment is that the free drug diffuses throughout the body and accumulates in the patient's skin and eyes, making them very sensitive to light," said Indrajit Roy, lead author and a postdoctoral researcher at the Institute for Lasers, Photonics and Biophotonics.
Following PDT, patients are cautioned to cover themselves as completely as possible when they go outside and even to avoid bright indoor light. Sunscreen provides little protection to a patient after PDT.
"With the nanoparticle that we have developed, the hydrophobic photosensitizing drugs can be dispersed more readily since they are encapsulated by a water-compatible shell," said Roy. "Once encapsulated, the drug remains inside the particle and is not released into the surrounding environment."
A key feature of the nanoparticle developed at UB, which measures about 35 nanometers, is the size of its pores, which the UB scientists designed to range between just .5 and 1.0 nanometers. A nanometer is one-billionth of a meter.
"The pore size allows oxygen to diffuse freely back and forth," said Roy.
That's critical because when laser light activates the photosensitizing drugs inside the nanoparticle, the drugs pass on the excess energy to molecular oxygen, converting it to singlet oxygen, which is highly toxic to cells.
"The singlet oxygen is what destroys the cancer cells," said Roy.
The ceramic-based nanoparticle is a member of a new class of materials known as Organically Modified Silica—or ORMOSIL—known for their extreme stability. These materials, Roy added, can be synthesized readily at ambient temperatures with the desired size, shape and porosity.
"By providing the flexibility of both surface modification and attachment, as well as encapsulation, the nanoparticle platform provides a new dimension to targeted drug delivery for a wide range of medical applications," said Paras Prasad, executive director of the Institute for Lasers, Photonics and Biophotonics, SUNY Distinguished Professor in the Department of Chemistry in College of Arts and Sciences, and a co-author of the paper.
The in vitro studies reported in the Journal of the American Chemical Society were conducted using the nanoparticles to encapsulate HPPH (2-devinyl-2-(a-hexyloxyethyl) pyropheophorbide, a photosensitizer now in clinical trials at RPCI.
In addition to Prasad and Roy, co-authors include Earl J. Bergey, deputy director of biophotonics at the Institute for Lasers, Photonics and Biophotonics; Thomas J. Dougherty, chief of photodynamic therapy at RPCI; Janet Morgan, cancer research scientist, II, in the Department of Dermatology at RPCI; Tymish Y. Ohulchanskyy and Haridas E. Pudavar postdoctoral associates in the UB Department of Chemistry, and Allan R. Oseroff, professor and chair of the Department of Dermatology in the School of Medicine and Biomedical Sciences.
The research was funded by grants from the U.S. Air Force through its Defense University Research Initiative on Nanotechnology (DURINT) and the National Institutes of Health.