Journal of Industrial and Engineering Chemistry, Vol.94, 498-506, February, 2021
Nitric oxide and reactive oxygen species-releasing polylactic acid monolith for enhanced photothermal therapy of osteosarcoma
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Photothermal therapy (PTT) has been extensively explored as a promising alternative therapeutic approach for many malignant tumors. However, PTT agents never repair bone defects because of their lack of osteogenic activity. Therefore, the integration of multi-modal therapies into one platform could show great promise in overcoming the drawbacks of conventional single-modal therapy and achieving improved therapeutic efficacy in cancer. In this study, an indocyanine green (ICG) and diethylenetriamine/nitric oxide adduct (DETA/NO)-loaded polylactic acid (PLA) (PLIN) monolith was created via simple thermally induced phase separation (TIPS) and used to enhance PTT efficacy by killing residual cancer cells and regenerating bone defects after surgical resection of tumor tissues. The resulting PLIN monolith exhibited interconnected microporous structures and uniform morphology composed of leaf-like small units. The results of in vitro PTT efficacy tests demonstrated that the PLIN monolith exhibited enhanced photothermal activity on osteosarcomas but did not caused phototoxicity in normal osteoblasts. The synergistic cancer therapy efficacy of PLIN was mainly caused by high local temperature and elevated intracellular generation of ONOO? in MG63 cells. In addition, PLIN induced significant apoptotic cell death following laser irradiation. Therefore, the PLIN monolith has potential for application in osteosarcoma therapy and bone regeneration.
Keywords:Photothermal therapy;Nitric oxide;Reactive oxygen species;Peroxynitrite;PLA monolith;Osteosarcoma
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