Nitric Oxide-Biosignal-Responsive Polypeptide Nanofilaments.

Nitric oxide (NO) is one of the three gasotransmitters in living organisms that relates to numerous biological signaling processes. The quest to smart molecular self-assembled systems with ideal NO-responsivity enables precise therapy and diagnosis of NO-associated diseases. Here we report a class of amphiphilic polypeptide containing an o -phenylenediamine-functionalized poly(l-glutamate) segment (PEOPA) that can respond to NO biosignal with extraordinary sensitivity and selectivity. Such polypeptides can further form a rigid filament nanostructure via the synergism of an α-helical secondary structure of PEOPA blocks and H-bonding between interchain OPA side groups. A biologically relevant level of NO can cleave the filament-forming OPA motifs, thus, leading to a dissociation of the assemblies. This NO-responsive disassembly behavior makes these polypeptide nanofilaments as NO-activated nanocarriers, which hold promise for NO-pathological milieu-specific drug delivery.