- Laboratory News
(Caroline de Gracia Lux, Enas Mahmoud, Shivanjali Joshi-Barr)
Many researchers intent on delivering drugs to specific disease conditions focus on targeting nanocarriers by attaching molecules to their surfaces that specifically bind molecules upregulated in a particular disease. However, this approach is expensive, and whether this strategy actually enhances delivery to intended locations is hotly debated. We sidestep this issue by focusing instead on the location of release, creating polymers that degrade in response to biochemical characteristics of disease.
We’ve created a polymeric nanoparticle intended to confine delivery to areas of inflammation by rapidly degrading in response to the combination of high concentrations of the reactive oxygen species hydrogen peroxide (which causes the polymer to solubilize) and low pH (which hydrolyzes it). We’ve also developed the first polymeric nanoparticle that releases its contents in response to the concentrations of peroxide that characterize oxidative stress and inflammation (~50 µM). This represents a major breakthrough, as many groups have been working towards this goal, which if combined with an imaging agent that's activated upon release, would allow detection of a state relevant to a broad range of diseases.
We haven’t focused solely on systems responsive to disease states; we’ve also created nanoparticles intended to address the challenge of delivery into the cytosol. Most polymeric delivery vehicles degrade slowly, so they’re transported back out of a cell through the endocytic pathway before their contents are released. Our nanoparticles allow contents to reach their cellular targets by degrading in a burst response to low pH, which likely causes the endosome to burst (artist rendering, right).