Affibody靶标金纳米颗粒对难治型甲状腺癌EGFR表达的光声成像研究

Refractory thyroid cancers(RTCs)are resistant to routine therapy with high mortality and poor prognosis.There are urgent need for novel theronostic strategies which could improve the recovery and survival rate. Targeted imaging toward RTC related biomarkers is beyond the reach of existing imaging modalities, hence it is necessary to establish targeted imaging platform which is based on advanced functional imaging technique,through which the early diagnosis of RTC and evalutaion for targeted therapy could be realized non-invasively. Photoacoustic imaging(PAI) and nanotechnology is attracting increasing attention in the field of molecular targeted imaging and translational medcine, they can provide structural and functional information simultaneously. EGFR and the activation of related signaling pathway have taken an important role in the proliferation, invasion and tumoral vascularization of RTC. This project is designed to label gold tripod like nanopartilce(Au-Tripod) with novel small scaffold protein Affibody,which could be specifically targeted to EGFR with high affinity.The characterization,optical absorption and pharmacodynamics of the Affibody-Au-Tripod will be evaluated; the in vitro and in vivo EGFR targeting ability will be studied and quantified through PAI study in RTC cellines and tumor modles; the feasibility of in vitro and in vivo EGFR targeted PAI with Affibody-Au-Tripod in RTC will be evalutaed. This project will establish a PAI platform for EGFR targeted imaging, which is promising in achieving non-invasive in vivo evaultion for EGFR positive RTC.

难治性甲状腺癌(Refractory thyroid cancer RTC)对常规治疗反应差、预后不良，致死率高，寻求RTC诊疗新策略对提高患者生存率意义重大，基于功能成像技术的分子靶向成像有望实现RTC的早期靶向诊断。光声成像技术与金纳米成像剂联合应用可同时提供结构和功能信息，是靶向成像和转化医学研究热点。EGFR及相关通路活化与RTC增殖、侵袭及新生血管形成密切相关，本研究拟选择EGFR为RTC分子成像靶点，应用与EGFR特异性结合的Affibody蛋白靶标鼎形金纳米，评估其理化、光学特性、生物相容性和药代学特点；通过光声成像定量评价其在不同RTC细胞系及相应裸鼠动物模型中的EGFR靶向结合能力；与对照、阻断组成像比较并其探讨在体内、体外水平对EGFR靶向光声成像的可行性。本项目有望实现RTC动物模型EGFR表达状态的活体无创性评估，为RTC早期诊断、靶向治疗及预后提供有效的评价手段。

难治性甲状腺癌(Refractory thyroid cancer RTC)对常规治疗反应差、预后不良，致死率高，寻求RTC诊疗新策略对提高患者生存率意义重大，基于功能成像技术的分子靶向成像有望实现RTC的早期靶向诊断。光声成像技术与金纳米成像剂联合应用可同时提供结构和功能信息，是靶向成像和转化医学研究热点。EGFR及相关通路活化与RTC增殖、侵袭及新生血管形成密切相关，本研究针对RTC分子成像靶点EGFR，应用与EGFR特异性结合的Affibody蛋白靶标鼎形金纳米，合成EGFR靶向成像探针，在对其理化、光学特性、生物相容性和药代学特点进行评估和研究之后，证实了其光声成像敏感性、低生物学毒性以及靶向成像稳定性；通过在裸鼠甲状腺滤泡癌动物模型中进行光声成像，评价该靶向探针的EGFR靶向结合及光声成像能力；通过对照、阻断组的成像比较，证实其在体内、体外水平对EGFR靶向光声成像具有较好的可行性。本项实现了RTC动物模型EGFR表达状态的活体无创性评估，为RTC早期诊断、靶向治疗及预后提供有效的评价手段。