Department of Chemistry and Chemical Biology, McMaster University , Hamilton, Ontario L8S 4M1, Canada.
Biomacromolecules. 2015 Sep 14;16(9):3033-41. doi: 10.1021/acs.biomac.5b00911. Epub 2015 Aug 31.
A fifth generation aliphatic polyester dendrimer was functionalized with vinyl groups at the periphery and a dipicolylamine Tc(I) chelate at the core. This structure was PEGylated with three different molecular weight mPEGs (mPEG160, mPEG350, and mPEG750) using thiol-ene click chemistry. The size of the resulting macromolecules was evaluated using dynamic light scattering, and it was found that the dendrimer functionalized with mPEG750 was molecularly dispersed in water, exhibiting a hydrodynamic diameter of 9.2 ± 2.1 nm. This PEGylated dendrimer was subsequently radiolabeled using (99m)Tc(CO)3(H2O)3 and purified to high (>99%) radiochemical purity. Imaging studies were initially performed on healthy rats to allow comparison to previous Tc-labeled dendrimers and then on xenograft murine tumor models, which collectively showed that the dendrimers circulated in the blood for an extended period of time (up to 24 h). Furthermore, the radiolabeled dendrimer accumulated in H520 xenograft tumors, which could be visualized by single-photon emission computed tomography (SPECT). The reported PEGylated aliphatic polyester dendrimers represent a new platform for developing tumor-targeted molecular imaging probes and therapeutics.
一种第五代脂肪族聚酯树枝状大分子被功能化，在外围带有乙烯基基团，在核心带有二吡啶甲胺 Tc(I)螯合物。该结构通过硫醇-烯点击化学用三种不同分子量的 mPEG（mPEG160、mPEG350 和 mPEG750）进行聚乙二醇化。使用动态光散射评估所得大分子的尺寸，发现用 mPEG750 功能化的树枝状大分子在水中呈分子分散状态，表现出 9.2±2.1nm 的水动力直径。随后，使用 (99m)Tc(CO)3(H2O)3对这种聚乙二醇化的树枝状大分子进行放射性标记，并通过高效 (>99%)放射化学纯度进行纯化。最初在健康大鼠中进行成像研究，以与之前标记的 Tc 树枝状大分子进行比较，然后在异种移植的鼠肿瘤模型中进行成像研究，这些研究共同表明，树枝状大分子在血液中循环的时间延长（长达 24 小时）。此外，放射性标记的树枝状大分子在 H520 异种移植肿瘤中积累，可以通过单光子发射计算机断层扫描 (SPECT)进行可视化。所报道的聚乙二醇化脂肪族聚酯树枝状大分子代表了开发肿瘤靶向分子成像探针和治疗剂的新平台。
