Chemotherapy is a conventional treatment method for metastatic bone cancer, but it has limitations, such as lower drug-targeting of bone tissues and serious side effects. Bone metastasis almost always occurs in advanced cancer, and most patients in this period have strong drug resistance, which further worsens the curative effect. To address the above-mentioned difficulties, a drug delivery platform is proposed in this paper that accomplishes the bone-targeting of drugs to efficiently inhibit tumors. First, the anti-cancer drugs 5-fluorouracil (5-Fu) and indocyanine green (ICG) were loaded into a zeolitic imidazolate framework (ZIF-90) to form 5-Fu/ICG@ZIF-90. Polyethylene glycol with zoledronic acid (ZOL) was encapsulated using 5-Fu/ICG@ZIF-90 to synthesize 5-Fu/ICG@ZIF-90-PEG-ZOL nanoparticles, which showed dimensional stability, good thermal stability, and bone-targeting ability. Second, the in vitro anti-cancer activity of the designed platform was investigated using cytotoxicity, apoptosis, live–dead staining, cell cycle, and cell ultrathin section analysis. The results indicated that the nanoparticles inhibited MCF-7 cell activity when chemotherapy was combined with PTT. Finally, H&E staining and TUNEL detection were performed in mouse organs and tumors. The nanoparticles combined with photothermal therapy (PTT) and triggered by near-infrared irradiation induce apoptosis of tumor cells in vivo, displaying a better efficacy of combined chemotherapy and photothermal therapy. Experiments conducted on the 5-Fu/ICG@ZIF-90-PEG-ZOL nanoparticles demonstrated their promising performance for cancer bone metastasis inhibition.
Recently, the combination of chemotherapy and chemodynamic therapy (CDT) has become a desirable strategy in the treatment of cancer. However, a satisfactory therapeutic outcome is often difficult to achieve due to the deficiency of endogenous H2O2 and O2 in the tumor microenvironment. In this study, a CaO2@DOX@Cu/ZIF-8 nanocomposite was prepared as a novel nanocatalytic platform to enable the combination of chemotherapy and CDT in cancer cells. The anticancer drug doxorubicin hydrochloride (DOX) was loaded onto calcium peroxide (CaO2) nanoparticles (NPs) to form CaO2@DOX, which was then encapsulated in a copper zeolitic imidazole ester MOF (Cu/ZIF-8) to form CaO2@DOX@Cu/ZIF-8 NPs. In the mildly acidic tumor microenvironment, CaO2@DOX@Cu/ZIF-8 NPs rapidly disintegrated, releasing CaO2, which reacted with water to generate H2O2 and O2 in the tumor microenvironment. The ability of CaO2@DOX@Cu/ZIF-8 NPs to combine chemotherapy and CDT was assessed by conducting cytotoxicity, living dead staining, cellular uptakes, H&E staining, and TUNEL assays in vitro and in vivo. The combination of chemotherapy and CDT of CaO2@DOX@Cu/ZIF-8 NPs had a more favorable tumor suppression effect than the nanomaterial precursors, which were not capable of the combined chemotherapy/CDT.
1 March 2021 in International Journal of Nanomedicine
Background: With the development of bacterial resistance, the range of effective antibiotics is increasingly becoming more limited. The effective use of nanoscale antimicrobial peptides (AP) in therapeutic and diagnostic methods is a strategy for new antibiotics. Methods: Combining both AP and cadmium selenide (CdSe) into a composite material may result in a reagent with novel properties, such as enhanced antibacterial activity, fluorescence and favorable stability in aqueous solution. Results: AP-loaded CdSe NPs (AP-CdSe NPs) showed strong antibacterial activity against multidrug-resistant (MDR) Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro and in vivo. Colony-forming unit (CFU) and minimum inhibitory concentration (MIC) assays showed that AP-CdSe NPs have highly effective antibacterial activity. The quantitative analysis of apoptosis by flow cytometry analysis further confirmed that MDR E. coli and S. aureus treated with AP-CdSe NPs had death rates of 98.76% and 99.13%, respectively. Also, AP-CdSe NPs was found to inhibit bacterial activity in an in vivo bacteremia model in mice infected with S. aureus. In addition, the antibacterial mechanism of AP-CdSe NPs was determined by RNA sequencing analysis. Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed the molecular mechanism of the antibacterial effect of AP-CdSe NPs. Importantly, histopathology analysis, and hematological toxicity analysis indicated that AP-CdSe NPs had few side effects. Conclusion: These results demonstrate that AP loaded on CdSe NPs had a higher water solubility, bioavailability and antibacterial effect compared with raw AP. This study reports findings that are helpful for the design and development of antibacterial treatment strategies based on AP.