"Solid tumors have a significantly lower extracellular pH, about 6.5-6.9, compared to normal tissue, which has an average pH of 7.4," Won said.
The weak polybases in the micelles contain molecules called amines, which are made of nitrogen and hydrogen atoms. The micelles swell at lower pH due to the increased "protonation," or the addition of protons to nitrogen atoms in the amines. Because the protons are positively charged, the like-charged amines repel each other, causing the nanoparticles to expand.
The positive charge slows the movement of micelles out of tumor tissue, which would cause the nanoparticles to accumulate inside the tumor mass long enough to enter tumor cells and release anticancer drugs.
"This concept is straightforward to understand, yet no one recognized it previously," Won said. "And it took us a while to put this description on a mathematical footing. To do that, we had to modify the famous Fick's first law diffusion equation."
The law, derived by physician and physiologist Adolf Fick in 1855, describes how molecules diffuse from regions of high concentration to regions of low concentration.
The micelles also are coated with protective varnish so that they might remain intact long enough to reach tumor sites, where they would expand and then biodegrade.
More research is needed to determine how well the approach could enhance drug delivery, but the pH phoresis concept developed by Won and his student represents a step in developing nanomedicine techniques in drug delivery, he said.
|Contact: Emil Venere|