醛酮还原酶AKR1C3是雄激素合成最后步骤关键酶，被视为前列腺癌向去势抵抗性前列腺癌（CRPC）转化的生物学标记和防治CRPC的潜在靶点。近年AKR1C3抑制剂研发虽取得一定进展，但靶向特异性AKR1C3抑制剂尚处于研究探索阶段。本项目前期工作显示，脂质体转染AKR1C3 siRNA，能减少细胞睾酮含量，抑制CRPC细胞增殖；对中药单体库筛选发现，小檗碱通过抑制AKR1C3酶活性，抑制CRPC细胞增殖。在此基础上，本项目拟采用纳米医学与RNA干涉技术相结合，构建以AKR1C3为靶点，以A10-3.2为导向分子的前列腺癌靶向特异性siRNA 干涉体系（APT-PEG-PAMAM/siAKR1C3），并在细胞水平全面评价该系统的稳定性、靶向性与有效性，初步观察全身给药后对前列腺癌小鼠模型的抑瘤作用。本研究将为AKR1C3 siRNA的体内应用及前列腺癌CRPC的治疗提供理论基础和实验依据。

As a key enzyme in the final two steps of androgen synthesis in human prostate cancer cells, aldo-keto reductase family 1 membr C3 (AKR1C3) has recently been regarded to be biomarker and potential anti-cancer drug target in castrate resistant prostate cancer (CRPC). Although there’s progression on AKR1C3 inhibitor researches, selective AKR1C3 inhibitors are still under investigation. Our prior study found that cellular testosterone and cell growth were significantly decrease by liposome transfection of AKR1C3; in our screening AKR1C3 inhibitors from traditional Chinese medicine (TCM) monomer library, we found berberine could decrease the formation of total testosterone (T) and inhibit the growth of CRPC cell line in a dose-dependent manner. Based on these studies, this project combines the nanomedicine and RNAi technology to synthese a novel nanocarrier with target head A10-3.2 to load siAKR1C3 (APT-PEG-PAMAM/siAKR1C3, APP/siRNA). And evaluating the stability of APP/siAKR1C3, the tumor-targeting therapeutic effect and the molecular mechanism of it on CRPC. The project develops the new strategy for the treatment of CRPC.