MultifunctionalNanocarrierTargetingSurvivinsiRNAInhibitsProliferation ofHepatocellularCarcinoma / 中山大学学报(医学科学版)

ABSTRACT

@#【Objective】 To investigate the inhibitory effect of RGD- modified，MRI visualized nanocarrier（RGD- PEG-g-PEI-SPION）targeting for Survivin siRNA（siRNA）delivery to hepatocellular carcinoma（HCC）in nude mice； and to investigate the MRI imaging function of RGD-PEG-g-PEI-SPION in nude mouse liver cancer. 【Methods】Nude mice were subcutaneously injected with Bel- 7402 cells to establish a subcutaneous tumor- bearing model. Tumor growth inhibition test，HE staining，immunohistochemical staining and tumor cell apoptosis test were used to evaluate the therapeutic effect of RGD-PEG-g-PEI-SPION targeted Survivin siRNA on liver cancer in nude mouse ；MRI imaging was used to analyze the targeting imaging function of RGD-PEG-g-PEI-SPION on hepatocellular carcinoma【Results】The subcutaneous tumor- bearing model of nude mice was successfully established，and the tumor volume of subcutaneous graft of RGD-PEG-g-PEI-SPION /siRNA，PEG-g-PEI-SPION/siRNA，RGD-PEG-g-PEI-SPION /siNC，PEG-g-PEI-SPION/ siNC and PBS solution in nude mice after first injection in the tail vein for 25 days was 59±8，156±7，202±7，212±9 and 220±8（mm3），respectively. Tumor histological examination showed that the RGD-PEG-g-PEI-SPION/siRNA group had the widest range of tumor necrosis，the lowest Survivin protein expression，and the number of apoptotic tumor cells significantly increased. Three hours after injection of RGD-PEG-g-PEI-SPION vector and PEG-g-PEI-SPION vector into the tail vein，the standardized MRI signal intensity of subcutaneous transplanted tumor decreased to（51.6±4.3）% and（88.5±3.2）% ，respectively ，compared with that before injection. 【Conclusion】 RGD- PEG- g- PEI- SPION delivers Survivin siRNA to hepatocellular carcinoma，promotes tumor cell apoptosis，inhibits tumor growth，and achieves good anti-tumor effect；RGD-PEG-g-PEI-SPION has a well targeted MRI imaging function in nude mouse liver cancer tissues.