Penn State researchers have developed a nontoxic nanoparticle that shows promise as an all-around effective delivery system for both therapeutic drugs and the fluorescent dyes that can track their delivery.
The researchers demonstrated that calcium phosphate particles ranging in size from 20 to 50 nanometers would successfully enter cells and dissolve harmlessly, and then release their cargo of drugs or dye.
In the study, led by Peter Butler, associate professor of bioengineering, the researchers used high-speed lasers to measure the size of fluorescent dye-containing particles from their diffusion in solution.
"We use a technique called time correlated single photon counting. This uses pulses of laser light to read the time, on the order of nanoseconds, that molecules fluoresce," said Butler.
Using the new method, the researchers could measure the size of the particles and their dispersion in solution, which in this case was a phosphate-buffered saline that is used as a simple model for blood.
"What we did in this study was to change the original neutral pH of the solution, which is similar to blood, to a more acidic environment, such as around solid tumors and in the parts of the cell that collect the nanoparticles-containing fluid immediately outside the cell membrane and bring it into the cell. When we lower the pH, the acidic environment dissolves the calcium phosphate particle," he added.
Butler explained: "We can see that the size of the particles gets very small, essentially down to the size of the free dye that was inside the particles. That gives us evidence that this pH change can be used as a mechanism to release any drug that is encapsulated in the particle."
Meant primarily for targeted cancer therapy, the tiny particles according to Butler could help in delivering various drugs that have been shown to inhibit cell growth associated with vascular disease.
Mark Kester, professor of pharmacology, and Jong Yun, associate professor of pharmacology, both at Penn State College of Medicine, optimized ceramide, a chemotherapeutic molecule that initiates cell death in cancer cells and known for its ability to slow growth in healthy cells, for both cancer and vascular disease.
It was found that by using human vascular smooth muscle cells in vitro, ceramide encapsulated in calcium phosphate nanoparticles reduced growth of muscle cells by up to 80 percent at a dose 25 times lower than ceramide administered freely, without damaging the cells.
Lead author Thomas Morgan, graduate student in chemistry said that the nanoparticles have several benefits that other drug delivery systems do not.
Unlike quantum dots, which are composed of toxic metals, calcium phosphate is a safe, naturally occurring mineral that already is present in substantial amounts in the bloodstream.
"What distinguishes our method are smaller particles (for uptake into cells), no agglomeration (particles are dispersed evenly in solution), and that we put drugs or dyes inside the particle where they are protected, rather than on the surface. For reasons we don't yet understand, fluorescent dyes encapsulated within our nanoparticles are four times brighter than free dyes," said Morgan.
The study is published in a recent online issue of Nano Letters.