Incorporating I-131 into a PAMAM (G5.0) dendrimerconjugate: design of a theranostic nanosensor for medullary thyroid carcinoma
Incorporating I-131 into a PAMAM (G5.0) dendrimerconjugate: design of a theranostic nanosensor for medullary thyroid carcinoma
复制标题
将 I-131 纳入 PAMAM (G5.0) 树枝状聚合物缀合物：甲状腺髓样癌治疗诊断纳米传感器的设计
DOI：
10.1039/c7ra00604g
复制
发表时间：
2017
期刊：
影响因子：
3.9
通讯作者：
Bossmann S. H.
中科院分区：
文献类型：
--
作者：
He R.;Wang H.;Su Y.;Chen C.;Xie L.;Chen L.;Yu J.;Toledo Y.;Abayaweera G. S.;Zhu G.;Bossmann S. H.
我们报告了通过将 131I 掺入 PAMAM (G5.0) 树枝状聚合物中，合成和纯化了甲状腺髓样癌 (MTC) 靶向探针。 131I 标记的对照树枝状大分子（131I-PAMAM (G5.0)，无附加靶向肽）和 MTC 靶向树枝状大分子（131I-PAMAM (G5.0)，附加有 VTP（血管靶向肽））均通过应用碘法用放射性同位素 131I 进行标记。通过超速离心纯化所得G5.0树枝状聚合物。通过纸色谱测定标记效率和放射化学纯度随时间的变化。 131I-PAMAM (G5.0) 和 131I-PAMAM (G5.0) 的放射性标记效率分别为 93 ± 1% 和 85 ± 2%。 131I-PAMAM (G5.0) 确实在标记后随时间的变化而表现出放射化学纯度虽小但显着的变化。观察到的最高纯度为 82 ± 2%。 131I–PAMAM (G5.0)–VTP 在标记后确实显示出放射化学纯度随时间的较大变化，最大为 80 ± 2%。体外观察了两种探针的稳定性及其与人甲状腺髓样癌细胞系（TT）的结合行为。与阴性对照组（由Na131I组成）相比，48小时和72小时时131I-PAMAM（G5.0）-VTP的TT细胞结合率显着增加（P < 0.01）。 48 h和72 h时131I-PAMAM(G5.0)-VTP的TT细胞结合率与阳性对照组(131I-PAMAM(G5.0)组)相比无显着性差异(P > 0.05)。这些发现已通过 MTT 测定得到证实。这些结果证实了早期的发现，即各种细胞类型都能快速摄取 PAMAM (G5.0)。
We report the synthesis and purification of a targeting probe for Medullary Thyroid Carcinoma (MTC) by incorporating 131I into PAMAM (G5.0) dendrimers. Both the 131I labeled control dendrimer (131I–PAMAM (G5.0) without attached targeting peptide) and the MTC-targeting dendrimer (131I–PAMAM (G5.0) attached to VTP (vascular targeting peptide)) were labeled with the radioisotope 131I by applying the iodogen method. The resulting G5.0 dendrimers were purified by means of ultracentrifugation. The labelling efficiencies and radiochemical purities vs. time were determined by paper chromatography. The radiolabeling efficiencies of 131I–PAMAM (G5.0) and 131I–PAMAM (G5.0) were 93 ± 1% and 85 ± 2%, respectively. 131I–PAMAM (G5.0) did exhibit small, but significant changes in radiochemical purity as a function of time after labelling. The highest observed highest purity was 82 ± 2%. 131I–PAMAM (G5.0)–VTP did display larger changes in radiochemical purity as a function of time after labelling, maximally 80 ± 2%. The stability of the two probes and their binding behavior to the human medullary thyroid cancer cell line (TT) were observed in vitro. Compared to the negative control group (consisting of Na131I), the TT cell binding rate of 131I–PAMAM (G5.0)–VTP was significantly increased at 48 h and 72 h (P < 0.01). The TT cell binding rate of 131I–PAMAM (G5.0)–VTP at 48 h and 72 h was not significantly different when compared to the positive control group (131I–PAMAM (G5.0) group) (P > 0.05). These findings have been confirmed by performing MTT assays. These results confirm earlier findings, which demonstrated fast uptake of PAMAM (G5.0) by various cell types.