Metal-organic framework IRMOFs coated with a temperaturesensitive gel delivering norcantharidin to treat liver cancer

BACKGROUND Norcantharidin(NCTD)is suitable for the treatment of primary liver cancer,especially early and middle primary liver cancer.This compound can reduce tumors and improve immune function.However,the side effects of NCTD have limited its application.There is a marked need to reduce the side effects and increase the efficacy of NCTD.AIM To develop a nanomaterial carrier,NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel(NCTD-IRMOF-3-Gel),aiming to improve the anticancer activity of NCTD and reduce the drug dose.METHODS NCTD-IRMOF-3-Gel was obtained by a coordination reaction.The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated.Cell cytotoxicity assays,flow cytometry,and apoptosis experiments in mouse hepatoma(Hepa1-6)cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models.RESULTS The particle size of NCTD-IRMOF-3-Gel was 50-100 nm,and the particle size distribution was uniform.The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect.The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation,and the inhibition rate increased with increasing drug concentration.By flow cytometry,NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases,and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest.Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells.CONCLUSION Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.

A guinea pig model of Ciwujia Injection-induced anaphylaxis for allergic substance screening

Objective: Though especially efficient for cardiovascular and cerebrovascular diseases treatment, many serious anaphylactic diseases could be induced by Ciwujia Injection(CWJI). However, study of the mechanism and detection of allergies have been investigated by the unknown sources of allergenic substances.In this study, a guinea pig model which could mimic the symptoms of anaphylactic reactions induced by Ciwujia Injection(CWJI) was modeled and used to screen the allergenic substance of CWJI.Methods: Guinea pigs were sensitized three times every other day with CWJI and excitated 14 d after the last sensitization administration. Then, the histamine, trypsin, IL-4 and IFN-γ levels, and the Annexin V positive rate of peritoneal mast cells(PMC) were detected, the numbers of B lymphocyte and the pathological changes were also analyzed to verify the guinea pig allergy model, PCA test and Ig E antibody levels were determined to study the mechanism.Results: The levels of total IgE, histamine, and trypsin were significantly increased after CWJI sensitization, IL-4 level was elevated, Annexin V positive of PMC cell rate, local skin reactions, and declined IFN-γwere observed after excitation. Histological examination showed that mild pathological changes in lungs were found.Conclusion: This guinea pig model may provide a powerful tool to study the mechanism in CWJI induced anaphylaxis and screen the allergic source of CWJI.