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

Lipeng Gao; Jinge Zhou; Jing Yu; Qilong Li; Xueying Liu; Lei Sun; Ting Peng; Jing Wang; Jianzhong Zhu; Jihong Sun; Weiyue Lu; Lei Yu; Zhiqiang Yan; Yiting Wang

doi:10.1038/s41598-017-03633-9

Scientific Reports (Jun 2017)

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

Lipeng Gao,
Jinge Zhou,
Jing Yu,
Qilong Li,
Xueying Liu,
Lei Sun,
Ting Peng,
Jing Wang,
Jianzhong Zhu,
Jihong Sun,
Weiyue Lu,
Lei Yu,
Zhiqiang Yan,
Yiting Wang

Affiliations

Lipeng Gao: 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
Jinge Zhou: 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
Jing Yu: 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
Qilong Li: 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
Xueying Liu: 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
Lei Sun: 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
Ting Peng: 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
Jing Wang: 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
Jianzhong Zhu: 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
Jihong Sun: Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
Weiyue Lu: Department of Pharmaceutics, School of Pharmacy, Fudan University, Ministry of Education
Lei Yu: 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
Zhiqiang Yan: 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
Yiting Wang: 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

DOI: https://doi.org/10.1038/s41598-017-03633-9
Journal volume & issue: Vol. 7, no. 1
pp. 1 – 13

Abstract

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Abstract 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 T1-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 (r1 = 18.98 mM−1S−1) was increased nearly 4.9 times compared with that of free Gd-DTPA (r1 = 3.87 mM−1S−1). 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.

Published in Scientific Reports

ISSN: 2045-2322 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Medicine; Science
Website: https://www.nature.com/srep/

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