Lu-Dendrimer Conjugated to Folate and Bombesin with Gold Nanoparticles in the Dendritic Cavity: A Potential Theranostic Radiopharmaceutical
Lu-Dendrimer Conjugated to Folate and Bombesin with Gold Nanoparticles in the Dendritic Cavity: A Potential Theranostic Radiopharmaceutical
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2016
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通讯作者：
Héctor Mendoza-Nava;G. Ferro-Flores;F. D. Ramírez;B. Ocampo-García;C. Santos-Cuevas;Liliana Aranda-Lara;E. Azorín-Vega;E. Morales-Ávila;K. Isaac-Olivé
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作者：
Héctor Mendoza-Nava;G. Ferro-Flores;F. D. Ramírez;B. Ocampo-García;C. Santos-Cuevas;Liliana Aranda-Lara;E. Azorín-Vega;E. Morales-Ávila;K. Isaac-Olivé
标记生物分子的Lu标记纳米粒子被认为是一类新型的治疗放射性药物。本研究的目的是合成树突状大分子(PAMAM-G4)-叶酸蛙素-金纳米粒子(AuNPs)，并评价其在靶向放射治疗和同时检测乳腺癌细胞中叶酸受体(FRs)和胃泌素释放肽受体(GRPR)过表达的放射药学潜力。在水碱性介质中，将P-SCN-苄基-DOTA偶联到树枝状大分子上。用HATU活化LysLys(DOTA)-蛙黄素和叶酸的羧酸基，并与树枝状大分子偶联，偶联物与1%HAuCl4混合，然后加入NaBH4，通过超滤进行纯化。进行了元素分析(EDS)、粒度分析(DLS)、透射电子显微镜分析、紫外-可见光谱、红外光谱和荧光光谱等测试。用LuCl3或GaCl3对偶联物进行标记，并用放射高效液相色谱法进行分析。研究证实树枝状大分子功能化具有很高的放化纯度(>；95%)。荧光结果表明，树枝状空腔中的AuNPs的存在为用于光学成像的放射性药物提供了有用的光物理性质。对T47D乳腺癌细胞的初步结合研究表明，细胞特异性摄取(41.15±2.72%)。Ludendrimer(AuNP)-叶酸-蛙素可作为高表达GRPR和FRS的乳腺肿瘤的光学和核显像剂，以及用于靶向放射治疗。
Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize Lu-dendrimer(PAMAM-G4)-folate-bombesin with gold nanoparticles (AuNPs) in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs) and gastrin-releasing peptide receptors (GRPRs) overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer. The carboxylate groups of LysLys(DOTA)-bombesin and folic acid were activatedwithHATUand also conjugated to the dendrimer.The conjugatewasmixedwith 1%HAuCl 4 followed by the addition of NaBH 4 and purified by ultrafiltration. Elemental analysis (EDS), particle size distribution (DLS), TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using LuCl 3 or GaCl 3 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%). Fluorescence results demonstrated that the presence of AuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15 ± 2.72%). Ludendrimer(AuNP)-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.