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

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-?-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.

SUBMITTER: Gao L

PROVIDER: S-EPMC5476566 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Gao Lipeng L Zhou Jinge J Yu Jing J Li Qilong Q Liu Xueying X Sun Lei L Peng Ting T Wang Jing J Zhu Jianzhong J Sun Jihong J Lu Weiyue W Yu Lei L Yan Zhiqiang Z Wang Yiting Y

Scientific reports 20170619 1

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<sub>1</sub>-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 ...[more]

PMID: 28630436

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Project description:Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of paclitaxel (PTX). High antitumor efficacy and low toxicity require that PTX mainly accumulated in tumors with little drug exposure to normal tissues. However, many PTX-loaded micelle formulations suffer from low stability, fast drug release, and lack of tumor-targeting capability in the circulation. To overcome these challenges, we developed a micellar formulation that consists of sodium cholate (NaC) and monomethoxy poly (ethylene glycol)-block-poly (d,l-lactide) (mPEG-PDLLA).PTX-loaded NaC-mPEG-PDLLA micelles (PTX-CMs) and PTX-loaded mPEG-PDLLA micelles (PTX-Ms) were formulated, and their characteristics, particle size, surface morphology, release behavior in vitro, pharmacokinetics and in vivo biodistributions were researched. In vitro and in vivo tumor inhibition effects were systematically investigated. Furthermore, the hemolysis and acute toxicity of PTX-CMs were also evaluated.The size of PTX-CMs was 53.61±0.75 nm and the ?-potential was -19.73±0.68 mV. PTX was released much slower from PTX-CMs than PTX-Ms in vitro. Compared with PTX-Ms, the cellular uptake of PTX-CMs was significantly reduced in macrophages and significantly increased in human cancer cells, and therefore, PTX-CMs showed strong growth inhibitory effects on human cancer cells. In vivo, the plasma AUC0-t of PTX-CMs was 1.8-fold higher than that of PTX-Ms, and 5.2-fold higher than that of Taxol. The biodistribution study indicated that more PTX-CMs were accumulated in tumor than PTX-Ms and Taxol. Furthermore, the significant antitumor efficacy of PTX-CMs was observed in mice bearing BEL-7402 hepatocellular carcinoma and A549 lung carcinoma. Results from drug safety assessment studies including acute toxicity and hemolysis test revealed that the PTX-CMs were safe for in vivo applications.These results strongly revealed that NaC-mPEG-PDLLA micelles can tumor-target delivery of PTX and enhance drug penetration in tumor, suggesting that NaC-mPEG-PDLLA micelles are promising nanocarrier systems for anticancer drugs delivery.

Dataset Information

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

Publications

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

Similar Datasets

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