Tong, Fei, Ye, Yicheng, Chen, Bin, Gao, Junbin, Liu, Lu, Ou, Juanfeng, van Hest, Jan C.M., Liu, Shuwen, Peng, Fei, Tu, Yingfeng, Tong, Fei, Ye, Yicheng, Chen, Bin, Gao, Junbin, Liu, Lu, Ou, Juanfeng, van Hest, Jan C.M., Liu, Shuwen, Peng, Fei, and Tu, Yingfeng
Cancer 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.