Nanoparticles that are responsive to the unique microenvironment of lesion sites have attracted
widespread attention in drug delivery. Herein, we report a new strategy for differential drug delivery to bacterial infection sites through the development of bacterial-responsive polymeric nanoparticles. With a convenient “arm first” procedure via one-step ring-opening polymerization, we developed a lipase-sensitive polymeric triple-layered and polyphosphoester core-crosslinked nanogel.