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A Multi-Functional Tumor Theranostic Nanoplatform for MRI Guided Photothermal-Chemotherapy

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Abstract

Purpose

To develop a multi-functional theranostic nanoplatform with increased tumor retention, improving antitumor efficacy and decreased side effects of chemotherapy drugs.

Methods

GO@Gd nanocomposites was synthesized via decorating gadolinium (Gd) nanoparticles (GdNP) onto graphene oxide (GO), and then functionalized by polyethylene glycol (PEG2000), folic acid (FA), a widely used tumor targeting molecule, was linked to GO@Gd-PEG, finally, doxorubicin (DOX) was loaded onto GO@Gd-PEG-FA and obtained a tumor-targeting drug delivery system (GO@Gd-PEG-FA/DOX). GO@Gd-PEG-FA/DOX was characterized and explored its theranostic applications both in a cultured MCF-7 cells and tumor-bearing mice.

Results

GO@Gd-PEG-FA/DOX could efficiently cross the cell membranes, lead to more apoptosis and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 7.6-fold higher DOX uptake of tumor than DOX. Besides, GO@Gd-PEG-FA/DOX also served as a powerful photothermal therapy (PTT) agent for thermal ablation of tumor and a strong T1-weighted contrast agent for tumor MRI diagnosis. The multi-functional nanoplatform also could selectively kill cancer cells in highly localized regions via the excellent tumor-targeting and MRI guided PTT abilities.

Conclusions

GO@Gd-PEG-FA/DOX exhibited excellent photothermal-chemotherapeutic efficacy, tumor-targeting property and tumor diagnostic ability.

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Abbreviations

DEG:

Diethylene glycol

DMEM:

Dulbecco modified eagle medium

DMSO:

Dimethyl sulfoxide

DOX:

Doxorubicin

EDC∙HCl:

N-(3-dimethylamino propyl-N0-ethylcar-bodiimide) hydrochloride

EG:

Ethylene glycol

FA:

Folic acid

Gd:

Gadolinium

GO:

Graphene oxide

NIR:

Near infrared

PEG2000:

Polyethylene glycol 2000

SRB:

Sulforhodamine B

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ACKNOWLEDGMENTS AND DISCLOSURES

The work is supported by grants from the National Natural Science Foundation of China (Nos.81273451, 81302717 and 81101684) and Postdoctoral Science Foundation of China (2015M582210).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Road, Zhengzhou, 450001, China

    Jinjin Shi, Binghua Wang, Zhaoyang Chen, Wei Liu, Jingjing Pan, Lin Hou & Zhenzhong Zhang

  2. Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, 450001, China

    Jinjin Shi, Binghua Wang, Zhaoyang Chen, Wei Liu, Jingjing Pan, Lin Hou & Zhenzhong Zhang

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  1. Jinjin Shi
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  2. Binghua Wang
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  3. Zhaoyang Chen
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  4. Wei Liu
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Correspondence to Lin Hou or Zhenzhong Zhang.

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Shi, J., Wang, B., Chen, Z. et al. A Multi-Functional Tumor Theranostic Nanoplatform for MRI Guided Photothermal-Chemotherapy. Pharm Res 33, 1472–1485 (2016). https://doi.org/10.1007/s11095-016-1891-7

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  • DOI: https://doi.org/10.1007/s11095-016-1891-7

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