Inflammation　is　a　critical　immune　response　to　various　stimuli　but　can　lead　to　diseases　when　uncontrolled.　Commonly　used　anti-inflammatory　drugs　usually　associated　with　side　effects,　natural　products　such　as　curcumin　(CUR)　have　emerged　as　a　promising　alternative　but　suffer　from　low　bioavailability.　This　study　introduces　a　novel　nanocarrier,　amphiphilic　hyperbranched　polyprodrug　(P(ACPP-co-CURMA)-b-POEGMA,　PACE),　designed　to　enhance　the　anti-inflammatory　activity　of　CUR.　PACE　micelles,　formed　from　a　hydrophobic　hyperbranched　polyprodrug　core　and　hydrophilic　POEGMA　corona,　demonstrated　remarkable　stability,　even　upon　dilution,　and　efficiently　released　CUR　in　response　to　the　reductive　intracellular　environment.　These　micelles　were　biocompatible　and　effectively　internalized　by　macrophages.　In　both　in　vitro　and　in　vivo　studies,　PACE　micelles　demonstrated　significant　anti-inflammatory　activity,　reducing　ROS　levels,　down-regulating　pro-inflammatory　cytokines,　and　alleviating　inflammation.　This　work　highlights　the　potential　of　PACE　micelles　as　a　promising　platform　for　targeted　and　responsive　anti-inflammatory　therapy,　with　implications　for　treating　inflammatory　disorders.　©　2023　The　Royal　Society　of　Chemistry.