Radionuclide (131)I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors.
Radionuclide (131)I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors.
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DOI：
10.1039/c5nr05585g
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发表时间：
2015-10
期刊：
影响因子：
6.7
通讯作者：
Jingyi Zhu;Lingzhou Zhao;Yongjun Cheng;Zhijuan Xiong;Yueqin Tang;Mingwu Shen;Jinhua Zhao;Xiangyang Shi
中科院分区：
文献类型：
--
作者：
Jingyi Zhu;Lingzhou Zhao;Yongjun Cheng;Zhijuan Xiong;Yueqin Tang;Mingwu Shen;Jinhua Zhao;Xiangyang Shi
我们报道了放射性(131)I标记的多功能树枝状大分子的合成、表征及其在肿瘤靶向单光子发射计算机断层扫描(SPECT)成像和放射治疗中的应用。在本研究中，用3-(4‘-羟基苯基)丙酸-OSU(HPAO)和叶酸(FA)与聚乙二醇(PEG)偶联，依次对5代端胺树枝状大分子(G5·NH2)进行了修饰，然后对树枝状大分子剩余的表面胺进行乙酰化修饰，标记了放射性碘131(131)I。用不同的方法对合成的多官能团(131)I-G5·NaAC-HPAO-PEGFA树枝状大分子进行了表征。我们发现，在~(131)I标记之前，G5·NaAC-HPAO-聚乙二醇-FA树状大分子在高达20μM的浓度下是无细胞毒性的，并且能够靶向过表达FA受体(FAR)的癌细胞，这要归功于修饰的FA配体。在苯酚基团存在下，放射性~(131)I能够以良好的稳定性和较高的放射化学纯度有效地标记到树枝状大分子平台上，并使该平台具有靶向SPECT成像和体内远高表达异种移植瘤模型的放射治疗能力。所设计的使用树枝状大分子纳米技术的策略可以扩展到开发各种放射性治疗纳米平台，用于靶向SPECT成像和不同类型癌症的放射治疗。
We report the synthesis, characterization, and utilization of radioactive (131)I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5·NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 ((131)I). The generated multifunctional (131)I-G5·NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to (131)I labeling, the G5·NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive (131)I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer.