211At标记的GIP靶向纳米载体用于神经内分泌肿瘤的治疗研究

神经内分泌肿瘤（NET）是一组起源于肽能神经元和神经内分泌细胞显著异质性的罕见肿瘤。NET起病隐袭临床诊断困难，常缺乏特异性治疗手段，预后差等特点。部分NET的生长抑制素受体表达低，无法使用奥曲肽受体放射性核素治疗。因此，开发新的靶向受体放射性核素治疗尤为重要。本项目通过制备半导体聚合物纳米颗粒，在表面修饰靶向多肽GIP，并标记211At用于GIPR过表达的神经内分泌肿瘤的α粒子治疗。半导体聚合物纳米颗粒具有长的血液循环和高的肿瘤富集，并且可以用于光声成像。GIP可以靶向到GIPR过表达的肿瘤细胞，通过优化GIP在纳米颗粒表面的密度来调节纳米颗粒对肿瘤细胞的亲和力。选择优化后的GIP修饰的靶向纳米颗粒标记211At用于神经内分泌肿瘤的治疗。通过本项目的实施，可望为临床恶性肿瘤患者提供具有潜在临床应用价值的治疗方法和策略。

Neuroendocrine tumors (NET) are a group of rare tumors that originate from the significantly heterogeneous peptidergic neuron and neuroendocrine cells. The clinical diagnosis of NET is difficult and lack of specific treatments which caused poor prognosis. Some NETs cannot be treated with octreotide receptor radionuclide therapy due to the low expression of somatostatin receptor. Therefore, it’s urgent to develop new peptide receptor radionuclide therapy. In this project, semiconductor polymer nanoparticles are prepared, with the surface modification of GIP and radiolabeled of 211At for targeted alpha particles therapy of GIPR overexpression of neuroendocrine tumors. Semiconductor polymer nanoparticles have long blood circulation and high tumor enrichment, and can be used for photoacoustic imaging. GIP can target to GIPR overexpressing tumor cells. The affinity of nanoparticles to tumor cells was adjusted by optimizing the density of GIP on the surface of nanoparticles. The optimized of GIP-modified nanoparticle with radiolabeled 211At was selected for the treatment of neuroendocrine tumors. Through the implementation of this project, it is expected to provide treatment methods and strategies with potential clinical application value for patients with GIP overexpression of NET.