Editors' ChoiceNanomedicine

Just Be “pH”-tient

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Science Translational Medicine  25 Jan 2012:
Vol. 4, Issue 118, pp. 118ec14
DOI: 10.1126/scitranslmed.3003734

During the American Revolutionary War, at the Battle of Bunker Hill, Colonel William Prescott gave his men this order: “Don’t fire until you see the whites of their eyes.” Owing to a shortage of ammunition, it was crucial that any shots taken were not wasted. Undoubtedly, disciplined obedience to the command helped to improve the efficiency of the defense.

Disciplined drug delivery can similarly improve therapeutic efficiency, as shown by Yoshitomi et al. in using pH-responsive nanoparticles to treat acute kidney injury. Nitroxide radicals, which scavenge reactive oxygen species (ROS), were covalently linked to a polymer with a pH-sensitive amino group. At a physiological pH of 7.4, the polymer strands assembled as micellar nanoparticles, which kept the nitroxide radical inactive inside the nanoparticle core. A decreased pH—as is found in acidic renal lesions—caused protonation of the amino linker group, leading to disruption of the nanoparticle structure. At that point, the nitroxide radicals were no longer restricted to the core and were free to scavenge ROS, which reduced inflammation and oxidative stress. The pH-responsive design prevented the nitroxide radicals from causing adverse effects in nontarget areas of the body.

Yoshimoto and colleagues tested these particles in a mouse model of acute kidney injury. Compared with free nitroxide radicals and control (non–pH-sensitive) particles, treating the animals with the pH-responsive particles resulted in lower levels of superoxide, less lipid oxidation, and reduced release of inflammatory cytokines. Furthermore, whereas the administration of free nitroxide radicals caused substantial reductions in blood pressure, this adverse effect was not seen with the pH-sensitive nanoparticles, showing that a little patience (in targeting the right tissues) can go a long way. This strategy to release ROS scavengers only within the range of their renal targets promises to improve the treatment of acute kidney injury.

T. Yoshitomi et al., The ROS scavenging and renal protective effects of pH-responsive nitroxide radical-containing nanoparticles. Biomaterials 32, 8021–8028 (2011). [PubMed]

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