Construction of a pH/TGase "Dual Key"-Responsive Gold Nanoradiosensitizer with Liver Tumor-Targeting Ability

Zhang, ZJ (Zhang, Zhenjie) 1Niu, XY (Niu, Xiaoyan) 1Feng, XY (Feng, Xiaoyue) 1Wang, XH (Wang, Xiaohui) 1Yu, LC (Yu, Licheng) 1Wang, W (Wang, Wei) 1Yuan, Z (Yuan, Zhi) 1

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ACS BIOMATERIALS SCIENCE & ENGINEERING, 2021, 7(7): 3434-3445

DOI 10.1021/acsbiomaterials.1c00428

Abstract

The method of tumor microenvironment (TME)-responsive aggregation has become a promising approach to enhance treatment effect by improving the accumulation of nanoparticles in tumors. The enzymatic cross-linking strategy has widely attracted attention owing to its good aggregation stability and biocompatibility. However, the enzymes in nontumor tissue can also catalyze the cross-linking reaction and reduce accumulation of nanoparticles in tumor. In this work, a "dual key"responsive strategy is utilized to construct a transglutaminase (TGase)/pH-responsive radiosensitizer (Au@TAcoGal) with specific aggregation behavior in hepatic tumor cells. Au@TAcoGal can retain its stability in blood circulation (pH 7.4) even in the presence of TGase in plasma. On reaching tumor sites, it can be endocytosed by hepatoma cells by the active targeting of phenylboronic acid (PBA) and aggregated under acidity and overexpression of TGase in cells. Due to its specific accumulation in hepatoma cells, radiotherapy can be operated under a lower dose of X-ray. The results show that the cellular accumulation of Au@TAcoGal increases by 30-70%, and the cell survival rate is less than 25% under X-ray irradiation. The antineoplastic results show that Au@TAcoGal exhibits a higher therapeutic effect, and the tumor inhibition rate can reach 84.21%.