A Targeted High-Z Nanoparticles Designed For External Radiotherapy Sensitization Of Solid Tumor In Vivo

1179 Background: Recently, there are plenty of studies about nanoparticles (NPs) of the high atomic number proposed as a radiotherapy sensitizer which induced the magnificent photoelectric effect in the radiotherapy. Despite the tremendous progress, the prognosis of solid tumor was still not optimistic so far because of the complicated tumor microenvironment. In our study, BaGdF5 NPs including two high atomic number elements (Ba,Gd) were designed as external radiotherapy sensitizer. Besides, the targeted RGD peptide which was connected with BaGdF5 could enhance the efficacy of radiotherapy simultaneously. Methods: BaGdF5 NPs were synthesized by hydrothermal method. The TEM, EDS, XRD,and MTT assay were performed to test the structure, property,and biocompatibility of NPs. The total of 12 nude mice bearing VX2 tumor were divided into four groups including Targeted NPs +RT (radiotherapy), NPs +RT, RT, and control group. After irradiating with X-ray of 8Gy, tumor volume growth curves of VX2 tumor in mice were delineated according to the obversation regularly to evaluate efficacy of NPs. Moreover, the tissues of treated VX2 tumors were harvested for corresponding histochemistry and immunohistochemistry which enrolled indexs that reflected the level of apoptosis and proliferating, such as Ki67 and Tunel. Results: The BaGdF5@PEG NPs was synthesized successfully and testified by TEM. The morphology of NPs was about 10nm in diameter, cobblestone-like, and homogeneous. There was no obvious cytotoxicity against HCT 116 cells in MTT assays. The tumor volume growth curves indicated that the inhibition effect of targeted NPs+RT was obviously elevated than those of NPs +RT, RT, and control groups. In latter three groups, the effects of radiotherapy sensitization were successively reduced. There was the same trend in apoptosis index based on positive expression of Ki67 staining and opposite trend of proliferating index based on positive expression of Tunel staining. Conclusions: The results indicated that the combination of high atomic number element NPs and targeted peptide significantly contributed to improving the effect of the radiotherapy sensitization. It is promising to be applied in radiotherapy of solid tumor in the further clinical applications. The mechanism of RGD@PEG -BaGdF5 need further exploration in the subcellular level.