中文摘要
骨肉瘤是骨骼系统最常见的原发性恶性肿瘤,临床药物治疗常因药物输送的困难而使治疗效果不佳。色素上皮源性因子(PEDF)是近年发现的强力抗肿瘤活性因子之一,可抑制骨肉瘤的生长与转移,很有希望成为治疗骨肉瘤的新药,但其确切作用机理尚不明确。因PEDF是内源性因子,研究外源性PEDF的体内抗肿瘤作用主要难题是给药途径。本课题拟借助表面键合转铁蛋白的免疫脂质体(IML)为载体,经反向跨膜主动装载PEDF,体内特异性靶向高表达转铁蛋白受体的骨肉瘤LM8细胞,定向输送外源性PEDF,并对其体内靶向活性、抗肿瘤血管生成、抑制肿瘤生长作用及作用机理进行分析研究,以助于阐明外源性PEDF的体内抗骨肉瘤作用机理,为今后探索安全、简易、无创性的骨肉瘤生物靶向治疗提供研究基础。
英文摘要
Osteosarcoma is primary malignant neoplasma which is often met in skeleton system. The clinical medicinal treatment is often of no effectiveness, because of poor drug delivery. Pigment epithelium-derived factor(PEDF) is one of the most antineoplasmic active factors which are found recently. It can restrain the growth and metastasis of osteosarcoma, and it is hopeful to become a new drug to cure osteosarcoma. But the exact mechanism of action is unclear. Because PEDF is an intrinsic factor, the administration route is the main difficulty to study the in vivo antineoplasms role of extrinsic PEDF. This topic is to draw the assistance from the carrier of transferrin surface linked immonoliposome(IML), to actively pack PEDF using inversion transmembrane technique, then specificly to target LM8 cell of osteosarcoma in vivo on the surface of which tranferrin receptors are highly expressed, and then targeting deliver extrinsic PEDF. Then to study the mechanism of it`s in vivo target activity, anti-vascularization of neoplams, and inhibition of tumor growth, to clarify the in vivo antiosteosarcoma role of extrinsic PEDF. This topic will be the base research perspectivly to explore a new targeting osteosarcoma therapeutical method which is safe, simple and non-invasive.
