Reduction Triggered<i>In Situ</i>Polymerization in Living Mice

"Smart" biomaterials that are responsive to physiological or biochemical stimuli have found many biomedical applications for tissue engineering, therapeutics, and molecular imaging. In this work, we describe <i>in situ</i> polymerization of activatable biorthogonal small molecules in response to a reducing environment change <i>in vivo</i>. We designed a carbohydrate linker- and cyanobenzothiazole-cysteine condensation reaction-based small molecule scaffold that can undergo rapid condensation reaction upon physiochemical changes (such as a reducing environment) to form polymers (pseudopolysaccharide). The fluorescent and photoacoustic properties of a fluorophore-tagged condensation scaffold before and after the transformation have been examined with a dual-modality optical imaging method. These results confirmed the <i>in situ</i> polymerization of this probe after both local and systemic administration in living mice.