Osteosarcoma　(OS)　remains　a　highly　aggressive　malignancy　in　adolescents,　characterized　by　rapid　metastasis,　poor　prognosis,　and　limited　response　to　conventional　treatments　such　as　surgery　and　chemotherapy,　largely　due　to　low　specificity,　severe　side　effects,　and　insufficient　control　of　metastatic　lesions.　The　tumor　microenvironment　(TME)　of　OS　features　high　GSH　levels　and　elevated　oxidative　stress,　making　it　particularly　susceptible　to　redox-based　therapies.　Strategies　that　amplify　reactive　oxygen　species　(ROS),　such　as　chemodynamic　therapy　(CDT)　and　photodynamic　therapy　(PDT),　offer　selective　tumor　destruction　and　overcome　conventional　treatment　limitations.　Herein,　we　report　a　copper-based　metal-organic　framework　(MOF)　nanoplatform,　Cu2O@CuHHTP@ZnPc@HA　(CCHZH),　featuring　a　hierarchical　core-shell　architecture　and　glutathione　(GSH)-responsive　degradability,　and　active　OS-targeting　capability.　The　nanoparticles　exhibited　a　uniform　hollow　spherical　structure　with　an　average　diameter　of　approximately　200　nm.　Leveraging　both　passive　targeting　via　the　enhanced　permeability　and　retention　(EPR)　effect　with　active　targeting　through　hyaluronic　acid　(HA)-CD44　interaction,　the　nanoparticles　accumulate　selectively　at　OS　sites,　subsequently　undergoing　GSH-triggered　disassembly　to　release　Cu+　ions　and　the　photosensitizer　ZnPc.　The　liberated　Cu+　initiates　Fenton-like　reactions,　generating　cytotoxic　hydroxyl　radicals　(center　dot　OH)　for　CDT,　while　ZnPc　produces　singlet　oxygen　(1O2)　under　670　nm　laser　irradiation　for　PDT.　This　dual-modal　reactive　oxygen　species　(ROS)　production　synergistically　disrupts　cellular　redox　homeostasis,　markedly　enhancing　oxidative　stress.　Mechanistically,　CCHZH　with　670　nm　laser　irradiation　activates　mitochondrial　apoptosis　via　the　Bax/Bcl-2/Caspase-3　signaling　axis　and　simultaneously　induces　cuproptosis　through　suppression　of　FDX1　and　LIAS　expression.　In　vitro,　CCHZH　reduced　cell　viability　to　10%　and　induced　80%　late　apoptosis,　as　confirmed　by　flow　cytometry.　Consistently,　in　vivo　evaluations　demonstrated　potent　therapeutic　efficacy　and　safety　in　subcutaneous,　orthotopic,　and　lung　metastasis　osteosarcoma　models.　Collectively,　our　study　introduces　a　targeted,　redox-responsive　nanoplatform　with　robust　CDT/PDT　synergy　and　dual-pathway　cell　death　induction,　providing　a　safe　and　effective　therapeutic　approach　for　OS.