骨肉瘤术后潜伏病灶复燃是影响远期治疗效果的核心问题。血管新生是骨肉瘤侵袭的重要机制，异常表达于脉管系统中的整合素可与胞外基质作用调控瘤细胞归巢。前一NSFC项目发现重组纤连蛋白/钙粘蛋白（rFN/CDH）可选择性激活αvβ3整合素，将其自组装于钙磷陶瓷的生物界面兼有骨传导和骨诱导特征。藉此假设：将紫杉醇通过纳米颗粒技术“嫁接”于前述自组装系统，可赋予成骨修复界面抗肿瘤特征。以此修复瘤缺损可通过rFN/CDH-αvβ3途径实现紫杉醇对瘤细胞的靶向募集和杀伤。拟制备紫杉醇-壳聚糖纳米颗粒进而构建[rFN/CDH-紫杉醇]自组装体，体内外观察对靶向募集肿瘤的杀伤效应。另共培养骨肉瘤细胞、血管相关细胞，从血管生成素旁分泌、受体酪氨酸激酶Tie2活化和ECM稳态等层次，了解以αvβ3整合素为核心的ECM重构分子事件及相关机制，以揭示血管相关细胞导致肿瘤细胞整合素差异表达，进而导致迁移能力改变的机理。

The main limitation after osetosarcoma resection is the recurrence caused by hidden satellite lesion. Previous study showed that angiogenesis was highly correlated to carcinogenesis, while over-expressed αvβ3 integrin in tumor vasculature contributed to the homing of cancer cells into their niches. Our previous NSFC grant reveals that rFN/CDH, as a specific activator of αvβ3 integrin, can be self-assembled into calcium phosphate ceramic and contribute to improved osteoconducive and osteoinductve properties. Hereby we postulate that when conjugated with chitosan (HGC) into nanoparticle, paclitaxel (PTX) can be incorporate in to calcium phosphate self-assembled system and exert anti-cancer performance. A PTX-HGC nanoparticle can be faricated for preparing [rFN/CDH-PTX] self-assembled nano-construct. Supplementary ex vivo and in vivo functional assays will be established to evaluate its anti-cancer functionality. Besides, the co-culture of osteosarcoma tumor cells and vessel-related cells will be employed to investigate the expression of angiopoietin, the activation of receptor tyrosine kinase Tie2, and ECM synthesis/degradation balance, which will togetherly reveal the molecular cascade and its possible mechanism orchesterd by αvβ3 integrin during ECM remodeling.As an expansion to our previous NSFC programme, this project could offer new insight into the relationship between integrin remodeling on tumor cell surface and their mobility.