ABSTRACT
This study aimed to construct an intelligent fluorescent nanocarrier for tumor cell tracing. Doxorubicin (DOX) was used as a model drug, and the gene targeting siBcl-2 was loaded to achieve synergistic inhibition of tumor cells. Mesoporous silicon nanoparticles (MSN) were prepared by a sol-gel method, and acetaldehyde cystine (AC) and polyethyleneimine (PEI) were covalently modified. The prepared nanocarrier MSN-AC-PEI was uniformly dispersed, with a particle size of 235.53 nm and a potential of 14.63 mV. The carrier material MSN-AC-PEI could load siRNA with the mass ratio of 60∶1 (Wvectors∶WsiRNA) and protect siRNA from RNase I degradation. To simulate the microenvironment of tumor, DOX release in phosphate buffer (pH 5) including 10 mmol·L-1 glutathione (GSH) was investigated. The cumulative release rate of DOX at 120 h is 35 times that of the normal physiological environment, which lays the foundation for the intelligent release of DOX in tumor cells. The results of cell experiments showed that the carrier material MSN-AC-PEI had significant green fluorescence, and the traceability can be maintained for 24 h after taken up by MCF-7 cells. After 24 hours of administration of the nano drug delivery system MSN-AC-PEI@DOX/siBcl-2, the inhibition rate of tumor cell proliferation reached 40.91%, and the late apoptosis rate was 60.84%. The Western blot results showed that compared with free DOX and siBcl-2, the nano-delivery system MSN-AC-PEI@DOX/siBcl-2 can significantly reduce the expression of anti-apoptotic protein Bcl-2, thereby enhancing its anti-tumor ability.
ABSTRACT
OBJECTIVE: To investigate the effect of moxibustion on the expression of IL-1beta, IL-2 and IL-6 proteins and mRNA in the cerebral cortex in tumor-bearing mice so as to study its mechanism underlying immunomodulation. METHODS: Forty Balb/c mice were randomly divided into control, tumor-bearing, non-acupoint moxibustion (N-AM) and acupoint-moxibustion (AM) groups (n = 10/group). Moxibustion was applied to "Dazhui" (GV 14), once every other day for 6 times. The expression of IL-1beta mRNA, IL-2 mRNA and IL-6 mRNA was detected by in situ hybridization, and the immunoactivity of IL-1beta, IL-6 and IL-2 determined by immunohistochemistry. RESULTS: Compared to the control group, the expression levels of IL-1beta mRNA and IL-2 mRNA, IL-1beta and IL-2 in the cerebral cortex of the tumor-bearing group were down-regulated significantly (P < 0.05, P < 0.01), while those of IL-6 mRNA and IL-6 up-regulated significantly (P < 0.05). Compared to the tumor-bearing group, the expression of IL-1beta mRNA and IL-2 mRNA, IL-1beta and IL-2 in the cerebral cortex in AM group were increased considerably (P < 0.05, P < 0.01); while cortical IL-6 immunoactivity in N-AM group was decreased significantly (P < 0.05), and IL-6 mRNA had no significant change in N-AM group (P > 0.05). Comparison between AM and N-AM groups showed that the expression levels of cortical IL-1beta mRNA and IL-2 mRNA, and IL-1beta and IL-2 proteins of the former group were obviously higher than those of the later group (P < 0.05, P < 0.01); while the immunoactivity of cortical IL-6 of AM group was significantly lower than that of N-AM group (P < 0.05). No significant difference between AM and N-AM groups in the expression of IL-6 mRNA (P > 0.05). CONCLUSION: Moxibustion treatment can up-regulate the expression of cortical IL-1beta mRNA, IL-2 mRNA, IL-1beta and IL-2 proteins, and down-regulate the expression of IL-6 mRNA and IL-6 in tumor-bearing mice, which may contribute to its effect in improving the immunosuppressing state under tumor conditions.
