Photo: Shining blue dye forming circle in black surrounding
Nanoparticles dissolved: the
fluorescent dye is released;
© Hari S. Muddana

Medical researchers are looking at any number of new methods to get drugs to specific locations in the body. In an article, a group of interdisciplinary scientists show that calcium phosphate particles ranging in size from 20 to 50 nanometers will successfully enter cells and dissolve harmlessly, releasing their cargo of drugs or dye.

Peter Butler, associate professor of bioengineering, 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,” Butler says. “This uses pulses of laser light to read the time, on the order of nanoseconds, that molecules fluoresce.” With this method his group was able to measure the size of the particles and their dispersion in solution, in this case 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 tumours 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. 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,” Butler explains.

The nanoparticles have several benefits other drug delivery systems do not, according to lead author Thomas Morgan. Calcium phosphate is a safe, naturally occurring mineral that already is present in substantial amounts in the bloodstream.

“What distinguishes our method is smaller particles for uptake into cells, the 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 do not yet understand, fluorescent dyes encapsulated within our nanoparticles are four times brighter than free dyes,” Morgan says. “Another advantage of encapsulation is that you need much less of them.”; Source: Penn State Materials Research Institute