Abstract：
Radionuclide-drug conjugates (RDCs) designed from small molecule or nanoplatform shows complementary characteristics. We constructed a new RDC system with integrated merits of small molecule and nanoplatform-based RDCs. Erlotinib was labeled with 131I to construct the bulk of RDC (131I-ER). Floxuridine was mixed with 131I-ER to develop a hydrogen bond-driving supermolecular RDC system (131I-ER-Fu NPs). The carrier-free 131I-ER-Fu NPs supermolecule not only demonstrated integrated merits of small molecule and nanoplatform-based RDC, including clear structure definition, stable quality control, prolonged circulation lifetime, enhanced tumor specificity and retention, and rapidly nontarget clearance, but also exhibited low biological toxicity and stronger antitumor effects. In vivo imaging also revealed its application for tumor localization of nonsmall cell lung cancer (NSCLC) and screening of patients suitable for epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. We considered that 131I-ER-Fu NPs showed potentials as an integrated platform for the radiotheranostics of NSCLC.
摘要：
由小分子或纳米平台设计的放射性核素-药物缀合物(RDC)显示出互补特性。我们构建了一种新的RDC系统，该系统具有基于小分子和纳米平台的RDC的综合优点。厄洛替尼用131I标记以构建大部分RDC(131I-ER)。将氟尿苷与131I-ER混合以形成氢键驱动的超分子RDC系统(131I-ER-FuNP)。无载体131I-ER-FuNP超分子不仅展示了小分子和基于纳米平台的RDC的综合优点，包括清晰的结构定义，稳定的质量控制，延长循环寿命，增强肿瘤特异性和保留，和快速的非目标清除，而且还表现出较低的生物毒性和较强的抗肿瘤作用。体内成像还揭示了其在非小细胞肺癌（NSCLC）的肿瘤定位和筛选适合表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKI）治疗的患者中的应用。我们认为131I-ER-FuNP具有作为非小细胞肺癌放疗综合平台的潜力。
