Figure 1.

Synthetic concept for the fabrication of poly(norbornene)-based nanogels. exo-N-(Methoxypoly(ethylene glycol)) norbornene-dicarboxyimide and exo-norbornene-carboxylic acid-pentafluorophenyl ester are block copolymerized under ring-opening metathesis conditions. The resulting amphiphilic reactive ester block copolymers self-assemble in DMSO into precursor micelles, whose cores can be functionalized by mono-amine-bearing entities, cross-linked with pH-(non)-degradable bisamines, and finally converted into fully hydrophilic nanogels. Ketal cross-linking promotes pH-responsive particle disassembly upon exposure to endolysosomal pH affording single, non-cross-linked soluble polymers.