MARCH 5, 2009--Scientists at the University of California, San Diego (San Diego, CA) say they have created fluorescing silicon nanoparticles that slowly release cancer drugs, then break down into harmless by-products. "It is the first luminescent nanoparticle that was purposely designed to minimize toxic side effects," said Michael Sailor, a chemistry, biochemistry and bioengineering professor who led the study, published in Nature Materials.
"This new design meets a growing need for non-toxic alternatives that have a chance to make it into the clinic to treat human patients," Sailor said.
The particles inherently glow red when illuminated with ultraviolet light. This effect is most commonly achieved by including toxic organic chemicals or quantum dots, which can leave behind potentially harmful heavy metals. They are made from thin wafers, made porous with an electrical current then smashed with ultrasound. Additional treatment alters the physical structure of the flakes to make them glow.
When the researchers tested their nanoparticles in mice, they saw tumors glow for several hours, then dim as the particles broke down. Levels dropped noticeably in a week and were undetectable after four weeks, they report. This is the first study to image tumors and organs using biodegradable silicon nanoparticles in live animals, the authors say.
Luminescent particles can reveal tumors too tiny to detect by other means or allow a surgeon to be sure all of a cancerous growth has been removed.
These nanoparticles could also help deliver drugs. The cancer drug doxorubicin will stick to the pores and slowly escape as the silicon dissolves. Targeted delivery would allow doctors to use smaller doses of the drug. At doses high enough to be effective, when delivered to the whole body, doxorubicin often has toxic side effects.
At about 100 nanometers, these particles are bigger than many designed to deliver drugs, which can be just a few nanometers across. Their larger size contributes to both their effectiveness (larger particles can hold larger drug doses) and their safety, the researchers say. Close examination of vulnerable organs like liver, spleen and kidney, which help to remove toxins, revealed no lasting changes in mice treated with the new nanoparticles.
Graduate students Ji-Ho Park and Luo Gu in Sailor's lab; Sangeeta Bhatia, bioengineering professor at the Massachusetts Institute of Technology and graduate student Geoffrey von Malzahn in Bhatia's lab; and Erkki Ruoslahti, professor at the University of California, Santa Barbara all contributed to this work.
See the paper, Biodegradable luminescent porous silicon nanoparticles for in vivo applications, in Nature Materials.