Tumor　microenvironment　(TME)　stimuli-responsive　nanoassemblies　are　emerging　as　promising　drug　delivery　systems　(DDSs),　which　acquire　controlled　release　by　structural　transformation　under　exogenous　stimulation.　However,　the　design　of　smart　stimuli-responsive　nanoplatforms　integrated　with　nanomaterials　to　achieve　complete　tumor　ablation　remains　challenging.　Therefore,　it　is　of　utmost　importance　to　develop　TME-based　stimuli-responsive　DDSs　to　enhance　drug-targeted　delivery　and　release　at　tumor　sites.　Herein,　we　proposed　an　appealing　strategy　to　construct　fluorescence-mediated　TME　stimulus-responsive　nanoplatforms　for　synergistic　cancer　therapy　by　assembling　photosensitizers　(PSs)　carbon　dots　(CDs),　chemotherapeutic　agent　ursolic　acid　(UA),　and　copper　ions　(Cu2+).　First,　UA　nanoparticles　(UA　NPs)　were　prepared　by　self-assembly　of　UA,　then　UA　NPs　were　assembled　with　CDs　via　hydrogen　bonding　force　to　obtain　UC　NPs.　After　combining　with　Cu2+,　the　resulting　particles　(named　UCCu2+　NPs)　exhibited　quenched　fluorescence　and　photosensitization　due　to　the　aggregation　of　UC　NPs.　Upon　entering　the　tumor　tissue,　the　photodynamic　therapy　(PDT)　and　the　fluorescence　function　of　UCCu2+　were　recovered　in　response　to　TME　stimulation.　The　introduction　of　Cu2+　triggered　the　charge　reversal　of　UCCu2+　NPs,　thereby　promoting　lysosomal　escape.　Furthermore,　Cu2+　resulted　in　additional　chemodynamic　therapy　(CDT)　capacity　by　reacting　with　hydrogen　peroxide　(H2O2)　as　well　as　by　consuming　glutathione　(GSH)　in　cancer　cells　through　a　redox　reaction,　hence　magnifying　intracellular　oxidative　stress　and　enhancing　the　therapeutic　efficacy　due　to　reactive　oxygen　species　(ROS)　therapy.　In　summary,　UCCu2+　NPs　provided　an　unprecedented　novel　approach　for　improving　the　therapeutic　efficacy　through　the　three-pronged　(chemotherapy,　phototherapy,　and　heat-reinforced　CDT)　attacks　to　achieve　synergistic　therapy.　©　2023