A Novel Gd-DTPA-conjugated Poly(L-γ-glutamyl-glutamine)-paclitaxel Polymeric Delivery System for Tumor Theranostics

• Published in: Scientific reports Vol. 7; no. 1; pp. 3799 - 13
• Main Authors: Gao, Lipeng, Zhou, Jinge, Yu, Jing, Li, Qilong, Liu, Xueying, Sun, Lei, Peng, Ting, Wang, Jing, Zhu, Jianzhong, Sun, Jihong, Lu, Weiyue, Yu, Lei, Yan, Zhiqiang, Wang, Yiting
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 19.06.2017; Nature Publishing Group UK; Nature Portfolio
• Subjects: Acids; Antitumor activity; Cancer therapies; Chemotherapy; Contrast agents; Drug delivery systems; Drugs; Glutamine; Laboratories; Lung cancer; Magnetic resonance imaging; Medical diagnosis; Nanoparticles; Paclitaxel; Polymers; Precision medicine; Radiation
• ISSN: 2045-2322; 2045-2322
• 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 mM S ) was increased nearly 4.9 times compared with that of free Gd-DTPA (r  = 3.87 mM S ). 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.