[Synthesis, characterization and antitumor activity of 5-fluorouracil-nicotinamide cocrystal].

Objective: To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to investigate its physicochemical and biological properties. Methods: The cocrystal of 5-Fu-NCT was prepared through the cooling technology. PXRD, NMR, FTIR and DSC were used to characterize the structure of 5-FU-NCT cocrystal. Solubility was measured by HPLC method. Drug resistant human liver cancer BEL-7402/5-FU cells were treated with 5-FU-NCT cocrystal, the inhibition effect was tested by MTT and HE staining, and cancer cell migration was determined by scratch test. Results: According to PXRD, NMR, FTIR and DSC results, the cocrystal of 5-Fu-NCT had been synthesized successfully. The characteristic diffraction peaks (2θ/°) of the cocrystal were 16.4, 20.4, 22.3, 27.9 and 30.1. The solubility of 5-FU-NCT was 13.5 g/L as measured by HPLC. The antitumor activity tests showed that 5-FU-NCT cocrystal enhanced anticancer effect of 5-FU, and the IC50 of 5-FU and 5-FU-NCT was 129.6 µg/mL and 42.6 µg/mL, respectively. Conclusion: 5-Fu-NCT cocrystal have been synthesized successfully through the cooling technology and it shows an enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU cells.

[Synthesis of BODIPY photosensitizers and their photodynamic effect on cancer cells].

Objective: To design and synthesize photosensitizers with different substituents and to identify its physicochemical characteritics and photodynamic effect on cancer cells. Methods: Two kinds of BODIPY photosensitizers BPOI and BPCI were synthesized through condensation reaction between aldehyde and reactive hydrogen of pyrrole, followed with electrophilic substitution reaction. Physicochemical properties were characterized by 1H NMR, FT-IR and UV-visible absorption spectra and fluorescence emission spectra. The ability to produce reactive oxygen species was detected by BPDF and DCFH-DA. Photodynamic therapy effect on rat glioma C6 cells in vitro was determined by MTT method. Results: Two kinds of BODIPY photosensitizers BPOI and BPCI were successfully synthesized with different substituents, which were confirmed by 1H NMR, FT-IR. Both materials had low toxicity and could be readily taken up by tumor cells. The ability of synthesized photosensitizers to produce reactive oxygen species was strongly influenced by solvent polarity when the substituent was electron-donating group, while no effect was found when the substituent was electron-withdrawing group. Conclusion: Photosensitizer BPOI with electron-donating substituent produces reactive oxygen species with a slow rate in a highly polar environment, while greatly enhanced this effect in a low polarity environment, which is expected to be used for environmental-selective photodynamic therapy in tumor cells.

[Bacterial outer membrane vesicles as nano carriers to study immunological activities].

Objective: To prepare a nano-carrier based on combining bacterial outer membrane vesicles (OMV) with three block polymer pluronic F127 (PEO100-PPO65-PEO100) (OMV-F127) and to investigate its immunological activity. Methods: Attenuated salmonella (sal) was cultivated. OMV were separated by centrifugal ultrafiltration or ultrasonication, and OMV-F127 was prepared by mechanical extrudation method. The protein contents and compositions were tested with BCA and SDS-PAGE; the morphology of OMV, F127 and OMV-F127 were observed with FM and TEM; the particle sizes and their zeta potential were determined with DLS. Mouse macrophage RAW246.7 cells were treated with OMV-F127 (50 µg/mL, 100 µg/mL) in vitro, and the concentrations of IL-12, TNF-α and IFN-γ in culture supernatant were measured with ELISA kits. Results: The contents of protein in separated OMV by centrifugal ultrafiltration and ultrasonication were 2.8 mg/mL and 2.7 mg/mL, respectively. SDS-PAGE showed the marker protein OmpF/C in OMV. Under the FM and TEM, ball-like structure of F127 and OMV-F127 was observed. Size analysis revealed that the diameters of OMV, F127 and OMV-F127 were 72±2 nm, 90±3 nm and 92±2 nm, respectively. ELISA tests revealed that OMV-F127 significantly stimulated the secretion of IL-12, TNF-α and IFN-γ in RAW246.7 cells. Conclusion: A nano-carrier based on bacterial outer membrane vesicles has been prepared, which can stimulate the secretion of cytokines and may have immunomodulatory effects.