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

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

Sci Rep. 2017 Jun 19;7(1):3799. doi: 10.1038/s41598-017-03633-9.

Authors

Lipeng Gao¹, Jinge Zhou¹, Jing Yu¹, Qilong Li¹, Xueying Liu¹, Lei Sun¹, Ting Peng¹, Jing Wang¹, Jianzhong Zhu¹, Jihong Sun², Weiyue Lu^{3

4}, Lei Yu¹, Zhiqiang Yan⁵, Yiting Wang⁶

Affiliations

¹ 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.
² Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China. braversun@sina.com.
³ Department of Pharmaceutics, School of Pharmacy, Fudan University, Ministry of Education, Shanghai, 201203, China.
⁴ Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai, 201203, China.
⁵ 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. zqyan@sat.ecnu.edu.cn.
⁶ 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. ytwang@nbic.ecnu.edu.cn.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Drug Delivery Systems / methods*
Gadolinium* / chemistry
Gadolinium* / pharmacology
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Paclitaxel / analogs & derivatives*
Paclitaxel / chemistry
Paclitaxel / pharmacology
Pentetic Acid* / chemistry
Pentetic Acid* / pharmacology
Polyglutamic Acid / analogs & derivatives*
Polyglutamic Acid / chemistry
Polyglutamic Acid / pharmacology
Theranostic Nanomedicine / methods*
Xenograft Model Antitumor Assays

Substances

Polyglutamic Acid
Pentetic Acid
Gadolinium
Paclitaxel
paclitaxel poliglumex