血管新生是肿瘤生长、转移和侵袭的重要因素。纳米硒能够通过抑制肿瘤血管新生、诱导细胞凋亡等方式阻断多种肿瘤的发生及发展。申请人曾报道，纳米硒复合物G2/PAH-Cit/SeNPs@siRNA能够降低肺癌细胞增殖 (Nanoscale,2014)，但其作用机制仍有待进一步完善。外泌体是天然的细胞间信使，能够向血管内皮细胞运送VEGF等细胞因子，影响其基因表达，促进肿瘤血管新生。申请人近期研究发现，G2/PAH-Cit/SeNPs@siRNA可减少肺癌细胞外泌体释放，并降低外泌体的促血管新生能力，提示其抑制血管新生的作用机制可能与外泌体有关。本项目拟利用细胞及动物模型阐明G2/PAH-Cit/SeNPs@siRNA对肺癌细胞外泌体的调控作用，明确其抑制血管新生的作用机制，并结合临床资料分析其临床价值。本项目成果将为开发纳米抗肿瘤血管新生药物提供新的理论指导。

Angiogenesis plays important roles in tumor growth, metastasis and invasion. Selenium nanoparticles efficiently interrupted tumorigenesis and tumor growth by antiangiogenesis and induce cell apoptosis. We have previously reported an selenium nanoparticle G2/PAH-Cit/SeNPs@siRNA ，shows antiproliferation effects on lung cancer (Nanoscale, 2014), but the mechanism is still undefined. Exosome, a natural nanocarrier and intercellular messenger, emerges as an important mediator in the process of vascular remodeling. They can serve as functional mediators in cell interaction leading to tumor angiogenesis. We recently found that of G2/PAH-Cit/SeNPs@siRNA significantly inhibit angiogenesis which induced by lung cancer derived exosomes. This result suggests a key role for exosomes in the molecular mechanism of angiogenesis. Based on this, we intended to investigate the effects and mechanisms of G2/PAH-Cit/SeNPs@siRNA inhibit angiogenic efficacy induced by lung cancer derived exosomes through cell and animal models. Furthermore, we will analyze the clinical relationship between exosomes and angiogenesis utilizing clinical materials. Thus, our research on the regulation and control between selenium nanoparticles and exosomes will provide theoretical and experimental basis for searching and developing new treatment methods of cancer angiogenesis.