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Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Affinity-Based Assembly of Peptides on Plasmonic Nanoparticles Delivered Intracellularly with Light Activated Control.
Bioconjugate Chemistry 2017 July 20
We report a universal strategy for functionalizing near-infrared light-responsive nanocarriers with both a peptide "cargo" and an orthogonal cell-penetrating peptide. Modularity of both the cargo and the internalization peptide attachment is an important feature of these materials relying on the robust affinity of polyhistidine tags to nitrilotriacetic acid in the presence of nickel as well as the affinity of biotin labeled peptides to streptavidin. Attachment to the gold surface uses thiol-labeled scaffolds terminated with the affinity partner. These materials allow for unprecedented spatiotemporal control over the release of the toxic α-helical amphipathic peptide (KLAKLAK)2 which disrupts mitochondrial membranes and initiates apoptotic cell death. Laser treatment at benign near-infrared wavelengths releases peptide from the gold surface as well as breaches the endosome barrier for cytosolic activity (with 105 -fold improved response to peptide activity over the free peptide) and can be monitored in real time.
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