NHEJ通路是电离辐射诱导的DNA损伤修复的关键通路，是肿瘤放射抵抗的主要机制。核酶Artemis通过与DNA-PKcs、DNA-LigaseⅣ的相继结合及伴随的磷酸化过程在NHEJ通路中发挥关键作用。本研究中，通过设计合成包含Artemis与DNA-PKcs、DNA-LigaseⅣ结合位点的肽段，并将其与具有肿瘤血管定位及穿胞能力的环形五肽CNGRC融合形成小分子融合多肽，首先研究融合多肽的生物学活性包括融合多肽对肿瘤细胞核的定位能力及细胞内代谢动力学，多肽对细胞放射敏感性及NHEJ修复效率的影响，然后研究多肽对Artemis与DNA-PKcs、DNA-LigaseⅣ结合的阻断作用等与其作用相关的细胞及分子机制，并进一步研究靶向融合多肽在体内实验中对移植瘤组织的靶向性和放射增敏效果，从而明确靶向Artemis的小分子融合多肽对肿瘤的放射增敏能力，为临床开发新的放射增敏剂建立基础。

Being the key pathway for irradiation-induced DNA damage repair, the NHEJ signaling pathway is the main mechanism for tumor radioresistance. Artemis, a phosphorylated protein with nuclease activity, plays a critical role in NHEJ pathway by binding with DNA-PKcs and DNA-LigaseⅣ successively and triggering the accompanying phosphorylation. In our study, we designed and synthesized various small peptides involving the binding sites of Artemis with DNA-PKcs or DNA-LigaseⅣ, and then combined them to a penta-peptide of CNGRC, which is able to localize tumor blood vessels and penetrate cell membrane. We studied the biological activity of the fusion polypeptide by taking into account its capability to enter nuclei, the intracellular metabolic kinetics, and its effects on cellular radiosensitivity and NHEJ efficiency. We then investigated fusion peptides’ blockage action on Artemis’s binding with DNA-PKcs or DNA-LigaseⅣ as well as their tumor radiosensitization effects, and explored the associated molecular mechanisms in vitro. Furthermore, we examined the tumor targeting and radiosensitization effect of the fusion peptides on transplanted tumor tissuses, thereby defining tumor radiosensitization potentiality of the peptides and laying the basis for developing new clinical tumor radiosensitizers.