功能化氧化石墨烯的靶向肿瘤成像与光热治疗

Functionalized nano-graphene oxide for cancer targeted imaging and photothermal therapy

整合素αvβ3是一种跨膜糖蛋白,高表达于多种肿瘤细胞表面,如人恶性胶质瘤(U87-MG).它能够作为一类肿瘤标志物,为肿瘤类型的诊断提供依据,并为肿瘤治疗提供潜在作用靶点.本文以人恶性胶质瘤细胞(U87-MG)为治疗模型,利用靶向配体——整合素αvβ3单克隆抗体(integrin αvβ3 monoclonal antibody),偶联新型纳米材料——氧化石墨烯(nano-graphene oxide,NGO),构建成一种新型纳米探针(NGO-mAb-FITC)用于靶向成像及光热治疗.这种纳米探针具有主动靶向功能,可识别αvβ3阳性表达细胞U87-MG,但不被αvβ3阴性表达的人乳腺癌细胞(MCF-7)摄取.通过异硫氰酸荧光素(FITC)共价修饰靶向配体,使纳米探针(NGO-mAb-FITC)获得对肿瘤细胞的靶向成像作用.同时,利用氧化石墨烯在808nm近红外激光照射下的光热转化性能,使得特异性摄取NGO-mAb-FITC纳米探针的肿瘤细胞内部产生过高热(hyperthermia),从而诱导肿瘤细胞热损伤及细胞凋亡.实验结果表明,NGO-mAb-FITC能有效识别靶细胞,为肿瘤诊断提供依据,而利用氧化石墨烯的高光热转换性能,为肿瘤治疗提供新途径,并有望成为一种有潜力的新型靶向光热转换探针而用于肿瘤的成像诊断与光热治疗.

Integrin αvβ3 is a heaterodimeric transmembrane receptor, overexpressed in some types of tumor cells such as glioblastoma U87-MG cells. Integrin αvβ3 as a tumor biomark, is widely used in cancer diagnosis and therapy. In this work we propose an active targeting nanocarrier system based on nano-graphene oxide （NGO-mAb-FITC） for imaging and photothermal therapy （PTT）, in which glioblastoma U87-MG cells are used as the model of tumor therapy. The nanoprobes efficiently target U87-MG cells （integrin αvβ3- positive）, with minimal influence on MCF-7 cells （integrin αvβ3-negative）. These NGO-mAb-FITC nanoprobes are then internalized into the αvβ3-positive tumor cells. Under 808 nm light irradiation, cells can be ablated by hyperthermia-induced apoptosis. The results indicate that the graphene oxide, a potential photothermal transduction nanoprobe, may potentially serve as a novel probe for cancer targeted imaging and therapy.