Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas
Chlorotoxin-Conjugated Multifunctional Dendrimers Labeled with Radionuclide 131I for Single Photon Emission Computed Tomography Imaging and Radiotherapy of Gliomas
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放射性核素 131I 标记的氯毒素偶联多功能树枝状聚合物用于神经胶质瘤的单光子发射计算机断层扫描成像和放射治疗
DOI：
10.1021/acsami.5b05836
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发表时间：
2015-09-09
影响因子：
9.5
通讯作者：
Zhao, Jinhua
中科院分区：
文献类型：
--
作者：
Zhao, Lingzhou;Zhu, Jingyi;Zhao, Jinhua
合成了用放射性核素“I”标记的氯毒素缀合的多功能树枝状聚合物，并将其用于癌症的靶向单光子发射计算机断层扫描（SPECT）成像和放射治疗。在本研究中，以第五代胺端聚（酰胺胺）树枝状大分子为平台，依次与聚乙二醇（PEG）、靶向剂氯毒素（CTX）和3-（4'-羟苯基）丙酸-OSu（HPAO）缀合。随后对剩余的树枝状聚合物末端胺进行乙酰化并用 I-131 进行放射性标记，以形成靶向治疗诊断树枝状聚合物纳米平台。我们表明，每个树枝状聚合物上具有约 7.7 个 CTX 和 21.1 个 HPAO 部分的树枝状聚合物平台在给定浓度范围（0-20 itM）内表现出出色的细胞相容性，并且由于附着的 CTX 可以特异性靶向过度表达基质金属肽酶 2 (MMP2) 的癌细胞。通过连接具有酚基团的 HPAO 部分，树枝状聚合物平台可以有效地用放射性 I-131 标记，具有良好的稳定性和高的放射化学纯度。重要的是，I-131 标记使树枝状聚合物平台能够用于体内 MMP2 过表达神经胶质瘤模型的靶向 SPECT 成像和放射治疗。开发的放射性标记多功能树枝状纳米平台可能有望用于人类神经胶质瘤的靶向治疗诊断。
Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide 'I were synthesized and utilized for targeted single photon emission computed tomography (SPECT) imaging and radiotherapy of cancer. In this study, generation five amine-terminated poly(amidoamine) dendrimers were used as a platform to be sequentially conjugated with polyethylene glycol (PEG), targeting agent chlorotoxin (CTX), and 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO). This was followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with I-131 to form the targeted theranostic dendrimeric nanoplatform. We show that the dendrimer platform possessing approximately 7.7 CTX and 21.1 HPAO moieties on each dendrimer displays excellent cyto compatibility in a given concentration range (0-20 itM) and can specifically target cancer cells overexpressing matrix metallopeptidase 2 (MMP2) due to the attached CTX. With the attached HPAO moiety having the phenol group, the dendrimer platform can be effectively labeled with radioactive I-131 with good stability and high radiochemical purity. Importantly, the I-131 labeling renders the dendrimer platform with an ability to be used for targeted SPECT imaging and radiotherapy of an MMP2-overexpressing glioma model in vivo. The developed radiolabeled multifunctional dendrirneric nanoplatform may hold great promise to be used for targeted theranostics of human gliomas.