Editors' ChoiceDrug Delivery

Nano keeps MK2 inhibitor intact and on target

Sci. Signal.  16 Jun 2015:
Vol. 8, Issue 381, pp. ec160
DOI: 10.1126/scisignal.aac7871

A peptide, called MK2i, that can penetrate cells and block the activity of MAPKAP kinase 2 (MK2) may be able to stop inflammation and fibrosis after vein grafting, but it has low bioavailability and is degraded easily once inside the cell. Evans et al. formulated MK2i in electrostatically complexed nanoparticles—nanopolyplexes—for delivery to vascular cells and tissues. Ex vivo, vascular smooth muscle cells and endothelial cells in human saphenous veins took up the MK2i nanopolyplexes, and the MK2i nanopolyplexes significantly inhibited neointima formation. In rabbit vein grafts, treatment with the MK2 nanopolyplexes prevented intimal hyperplasia for 1 month after transplant; in contrast, free MK2i peptide had no effect. Thus, complexing the MK2 inhibitor peptide with an endosomolytic polymer could improve long-term graft patency. Both treatments blocked macrophage recruitment or signaling or both in vivo, which could possibly lead to less inflammation. In human saphenous veins, the MK2i nanopolyplexes similarly reduced proinflammatory cytokines and reduced vascular smooth muscle cell migration. This nanoencapsulation approach may be broadly applied to other therapeutic cell-penetrating peptides to prolong bioavailability and enhance stability in vivo.

B. C. Evans, K. M. Hocking, M. J. Osgood, I. Voskresensky, J. Dmowska, K. V. Kilchrist, C. M. Brophy, C. L. Duvall, MK2 inhibitory peptide delivered in nanopolyplexes prevents vascular graft intimal hyperplasia. Sci. Transl. Med. 7, 291ra95 (2015). [Abstract]