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lüll Bone-Targeting Prodrug Mesoporous Silica-Based Nanoreactor with Reactive Oxygen Species Burst for Enhanced Chemotherapy Tong F; Ye Y; Chen B; Gao J; Liu L; Ou J; van Hest JCM; Liu S; Peng F; Tu YACS Appl Mater Interfaces 2020[Aug]; 12 (31): 34630-34642Cancer remains a primary threat to human lives. Recently, amplification of tumor-associated reactive oxygen species (ROS) has been used as a boosting strategy to improve tumor therapy. Here, we report on a bone-targeting prodrug mesoporous silica-based nanoreactor for combined photodynamic therapy (PDT) and enhanced chemotherapy for osteosarcoma. Because of surface modification of a bone-targeting biphosphate moiety and the enhanced permeability and retention effect, the formed nanoreactor shows efficient accumulation in osteosarcoma and exhibits long-term retention in the tumor microenvironment. Upon laser irradiation, the loaded photosensitizer chlorin e6 (Ce6) produces in situ ROS, which not only works for PDT but also functions as a trigger for controlled release of doxorubicin (DOX) and doxycycline (DOXY) from the prodrugs based on a thioketal (TK) linkage. The released DOXY further promotes ROS production, thus perpetuating subsequent DOX/DOXY release and ROS burst. The ROS amplification induces long-term high oxidative stress, which increases the sensitivity of the osteosarcoma to chemotherapy, therefore resulting in enhanced tumor cell inhibition and apoptosis. The as-developed nanoreactor with combined PDT and enhanced chemotherapy based on ROS amplification shows significant promise as a potential platform for cancer treatment.|Antibiotics, Antineoplastic/chemistry/*pharmacology[MESH]|Apoptosis/drug effects[MESH]|Cell Cycle/drug effects[MESH]|Cell Proliferation/drug effects[MESH]|Doxorubicin/chemistry/*pharmacology[MESH]|Doxycycline/chemistry/*pharmacology[MESH]|Drug Screening Assays, Antitumor[MESH]|Humans[MESH]|Nanoparticles/chemistry[MESH]|Oxidative Stress/drug effects[MESH]|Particle Size[MESH]|Photochemotherapy[MESH]|Photosensitizing Agents/chemistry/*pharmacology[MESH]|Porosity[MESH]|Prodrugs/chemistry/*pharmacology[MESH]|Reactive Oxygen Species/*metabolism[MESH]|Silicon Dioxide/chemistry[MESH]|Surface Properties[MESH]|Tumor Cells, Cultured[MESH] |