Doxorubicin-Loaded MnO(2)@Zeolitic Imidazolate Framework-8 Nanoparticles as a Chemophotothermal System for Lung Cancer Therapy

[Image: see text] Doxorubicin-loaded MnO(2)@zeolitic imidazolate framework-8 (DOX/MnO(2)@ZIF-8) nanoparticles, a smart multifunctional therapeutic platform, were prepared for the treatment of lung cancer. The morphology, structure, and redox and photothermal properties of MnO(2)@ZIF-8 were characterized by the corresponding methods. The anticancer drug DOX released from the DOX/MnO(2)@ZIF-8 nanoparticles was measured. The cell viability of Lewis lung cancer (LLC) cells treated with MnO(2)@ZIF-8 or DOX/MnO(2)@ZIF-8 nanoparticles was determined using the cell counting kit-8 (CCK-8) method. The cellular uptake of DOX/MnO(2)@ZIF-8 nanoparticles into LLC cells was observed using a confocal laser scanning microscope. TUNEL staining was performed to evaluate the in vivo therapeutic efficacy of DOX/MnO(2)@ZIF-8 nanoparticles. The results showed that the as-prepared MnO(2)@ZIF-8 nanoparticles had an average particle size of 155.59 ± 13.61 nm and the DOX loading efficiency was 12 wt %. MnO(2)@ZIF-8 could react with H(2)O(2) to generate O(2) and showed a great photothermal conversion effect both in vitro and in vivo. Up to 82% of total DOX could be released from DOX/MnO(2)@ZIF-8 nanoparticles at pH = 5.0. The CCK-8 assay showed that MnO(2)@ZIF-8 had low cytotoxicity to LLC cells, while DOX/MnO(2)@ZIF-8 can significantly reduce the cell viability. DOX/MnO(2)@ZIF-8 can be accumulated in LLC cells over time. Compared with PBS and DOX/MnO(2)@ZIF-8 groups, the mice in the DOX/MnO(2)@ZIF-8 + NIR group had the most apoptotic cells and significantly reduced tumor volume. In conclusion, these findings suggest that the as-prepared MnO(2)@ZIF-8 nanoparticles with synergetic therapeutic effects by photothermal therapy and improved tumor microenvironment and as a pH-responsive nanocarrier for delivering the nonspecific anticancer drug DOX might be applied in the treatment of lung cancer.