Few things in life are more debilitating than a chronic disease, and these conditions are even more mentally draining for patients when their cause is mysterious. Take, for instance, the collection of conditions known as inflammatory bowel diseases (IBDs). In the United States, some 60,000 individuals are diagnosed with IBDs each year, and a total of about 3 million individuals are living with the disease. Why the body suddenly sets off this painful and incapacitating inflammation of the gastrointestinal tract is not clearly understood, but it seems to involve aberrant signaling by cytokines, molecules that can act as danger signals to immune cells.
The size and shape of a negatively charged, or anionic, hydrogel (shown as black crossed lines at center) changes with pH. The hydrogel takes up positively charged nanoparticles (purple spheres) containing a therapeutic agent, in this case a small-interfering RNA (siRNA) that can silence troublesome genes associated with irritable bowel diseases. In the acidic environment of the gastrointestinal tract, the hydrogel has a small mesh size and protects its therapeutic payload from the harsh environment. Once the hydrogel transits to the intestine, the pH level increases, which causes the hydrogel to swell (or decomplex); its mesh size increases and it releases its nanoparticle payload only in this target environment. The nanoparticles have a molecular group, called a moiety, that binds to the receptor of macrophage cells in the small intestine. The nanoparticles are taken into the cell by phagocytosis, where they swell because of their positive (or cationic) charge and then release their siRNA payload into the cytosol, the aqueous component of the cytoplasm of a cell.
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