Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.
Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
Sci Rep. 2017 Jun 19;7(1):3799. doi: 10.1038/s41598-017-03633-9.
The conventional chemotherapeutics could not be traced in vivo and provide timely feedback on the clinical effectiveness of drugs. In this study, poly(L-γ-glutamyl-glutamine)-paclitaxel (PGG-PTX), as a model polymer, was chemically conjugated with Gd-DTPA (Gd-diethylenetriaminepentaacetic acid), a T-contrast agent of MRI, to prepare a Gd-DTPA-conjugated PGG-PTX (PGG-PTX-DTPA-Gd) delivery system used for tumor theranostics. PGG-PTX-DTPA-Gd can be self-assembled to NPs in water with a z-average hydrodynamic diameter about 35.9 nm. The 3 T MRI results confirmed that the relaxivity of PGG-PTX-DTPA-Gd NPs (r = 18.98 mMS) was increased nearly 4.9 times compared with that of free Gd-DTPA (r = 3.87 mMS). The in vivo fluorescence imaging results showed that PGG-PTX-DTPA-Gd NPs could be accumulated in the tumor tissue of NCI-H460 lung cancer animal model by EPR effect, which was similar to PGG-PTX NPs. The MRI results showed that compared with free Gd-DTPA, PGG-PTX-DTPA-Gd NPs showed significantly enhanced and prolonged signal intensity in tumor tissue, which should be attributed to the increased relaxivity and tumor accumulation. PGG-PTX-DTPA-Gd NPs also showed effective antitumor effect in vivo. These results indicated that PGG-PTX-DTPA-Gd NPs are an effective delivery system for tumor theranostics, and should have a potential value in personalized treatment of tumor.
传统的化疗药物在体内无法追踪，无法及时反馈药物的临床疗效。在这项研究中，聚（L-γ-谷氨酰-L-谷氨酰胺）-紫杉醇（PGG-PTX）作为一种模型聚合物，与 Gd-二乙三胺五乙酸（Gd-二乙烯三胺五乙酸）（MRI 的 T1 造影剂）进行化学偶联，制备了 Gd-二乙三胺五乙酸偶联的 PGG-PTX（PGG-PTX-DTPA-Gd）递药系统，用于肿瘤治疗。PGG-PTX-DTPA-Gd 可以在水中自组装成 NPs，其水动力直径约为 35.9nm。3T MRI 结果证实，PGG-PTX-DTPA-Gd NPs 的弛豫率（r=18.98mMS）比游离 Gd-DTPA（r=3.87mMS）增加了近 4.9 倍。体内荧光成像结果表明，PGG-PTX-DTPA-Gd NPs 可以通过 EPR 效应在 NCI-H460 肺癌动物模型的肿瘤组织中积累，这与 PGG-PTX NPs 相似。MRI 结果表明，与游离 Gd-DTPA 相比，PGG-PTX-DTPA-Gd NPs 在肿瘤组织中的信号强度增强和延长程度明显，这应归因于弛豫率的提高和肿瘤的积累。PGG-PTX-DTPA-Gd NPs 也在体内表现出有效的抗肿瘤作用。这些结果表明，PGG-PTX-DTPA-Gd NPs 是一种有效的肿瘤治疗递药系统，在肿瘤的个体化治疗中具有潜在的应用价值。
