骨肉瘤是骨骼中最常见的恶性肿瘤，原发性骨肉瘤主要发生在15岁左右的青少年，致残致死率高，目前的治疗方法虽取得一定效果，但对转移或肿瘤复发病人，总体五年生存率仍不足20%，因此，研究骨肉瘤的新疗法依然必要和迫切。表观遗传因素在骨肉瘤的发生发展中起着非常重要的作用，本项目依据现有的文献研究成果和项目组在核酸递送载体构建方面的工作以及在骨肉瘤细胞中筛选出低表达、具有潜在抗瘤作用的circRNA等提出：“构建多功能骨肿瘤响应性阳离子载体用于高效递送circRNA并可抑制骨肉瘤的增殖侵袭转移”，为验证该设想，项目采用载体构建、细胞分子生物学、生物信息学等先进技术，研究多功能阳离子载体合成及其分子结构与生物学性能之间的构效关系，筛选并研究目标circRNA调控骨肉瘤的机制，阐明骨肿瘤响应性多功能阳离子载体/circRNA在体内外的作用机制。项目如成功实施可为探索骨肉瘤治疗新方法提供科学与实验依据。

Osteosarcoma is the most common malignant tumor in bone. The primary osteosarcoma mainly occurs in adolescents aged around 15 years old with a high disability rate and mortality rate. Although the current treatment has achieved certain beneficial effects, the overall five-year survival rate is still less than 20% for patients with metastasis or recurrence, so there is still a long way to find other effective treatments. Epigenetic factors play a very important role in the occurrence and development of osteosarcoma. Based on the existing literatures, the achievements of the project team in the construction of nucleic acid carrier and the results from our circRNA microarray, we proposes the hypothesis " the constructed multifunctional cationic carrier can efficiently deliver circRNA and suppress the cell proliferation, invasion and metastasis of osteosarcoma." To verify that, this project will adopt advanced technologies in materials science, molecular biology and bioinformatics to study the principal of the structure-activity relationship between the molecular structures and biological performances of multi-functional cationic carriers, to screen the potential anti-osteosarcoma circRNA and verify the underlying therapeutic mechanism in vitro and in vivo. Successful implementation of the project can provide scientific and experimental basis for exploring new treatments for osteosarcoma.