Peroxynitrite (ONOO-) Redox Signaling Molecule-Responsive Polymersomes.

Designing specific-responsive polymer nanocapsules toward a definite cell signaling molecule for targeted therapy faces a great challenge. Here we demonstrate that new block copolymer appended trifluoromethyl ketone side groups can chemoselectively respond to an endogenous redox biosignal, peroxynitrite (ONOO-), but shield the interference of other biogenic reactive oxygen, nitrogen, and sulfur species (ROS/RNS/RSS). The ONOO- signaling molecule is capable of triggering cascade oxidation-elimination reactions to cleave the side functionalities from the polymer chain, which induces a large alteration of the polymer amphiphilicity and further leads to controllable disassembly of their self-assembled vesicular structure. Modulating the ONOO- stimulus concentrations could readily control the vesicle dissociation rates for desirable drug delivery. We envisage that this polymer model would provide a new scenario to construct bioresponsive macromolecular systems for future biomedical nanotechnologies.