In this work, a fluoroquinolone antibiotic drug (sparfloxacin (SP)) was selected as a chemotherapy drug and photosensitizer for combined therapy. A facile chemical process was developed to incorporate SP and upconversion nanoparticles (UCNPs) into the thermally sensitive amphiphilic polymer polyethylene glycol-poly(2-hexoxy-2-oxo-1,3,2-dioxaphospholane). In vitro and in vivo experiments showed that 60% of the SP molecules can be released from the micelles of thermal-sensitive polymers using a 1 W cm −2 980 nm laser, and this successfully inhibits cell migration and metastasis by inhibiting type II topoisomerases in nuclei. Additionally, intracellular metal ions were chelated by SP to induce cancer cell apoptosis by decreasing the activity of superoxide dismutase and catalase. In particular, the fluoroquinolone molecules produced singlet oxygen ( 1 O 2 ) to kill cancer cells, and this was triggered by UCNPs when irradiation was performed with a 980 nm laser. Overall, SP retained a weak chemotherapeutic effect, achieved enhanced photosensitizer-like effects, and was able to repurpose old drugs to elevate the therapeutic efficacy against cancer, increase the specificity for suppressing tumor migration and proliferation, and enhance apoptosis.

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