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Redox-responsive hyaluronic acid-functionalized graphene oxide nanosheets for targeted delivery of water-insoluble cancer drugs

Authors Liu J, Zhang D, Lian S, Zheng J, Li B, Li T, Jia L

Received 11 May 2018

Accepted for publication 3 July 2018

Published 14 November 2018 Volume 2018:13 Pages 7457—7472

DOI https://doi.org/10.2147/IJN.S173889

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Jiang Yang

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Jian Liu,1,2 Doudou Zhang,1,2 Shu Lian,1,2 Junxia Zheng,1,2 Bifei Li,1,2 Tao Li,1,2 Lee Jia1,2

1Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou 350002, China; 2Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350002, China

Background: Gefitinib (Gef), an important epidermal growth factor receptor (EGFR), is used to treat lung cancer, but low water solubility and poor bioavailability severely limit its application in cancer therapy.
Methods: In this study, nano-graphene oxide (NGO) was decorated with hyaluronic acid (HA) by a linker cystamine dihydrochloride containing disulfide bonds (-SS-), followed by the incorporation of gefitinib, thus, constructing a HA-functionalized GO-based gefitinib delivery system (NGO-SS-HA-Gef). Subsequently, studies of biological experiments in vitro and in vivo were performed to investigate the therapeutic effect of the system in lung cancer.
Results: The HA-grafted GO nanosheets possessed enhanced physiological stability, admirable biocompatibility, and no obvious side effects in mice and could act as a nanocarrier for the delivery of gefitinib to tumor. Cellular uptake and intracellular cargo release assays showed that the uptake of NGO-SS-HA by A549 cells was facilitated via CD44 receptor-mediated endocytosis, and that more drug was released from NGO-SS-HA in the presence of GSH than in the absence of GSH. The target-specific binding of NGO-SS-HA to cancer cells with redox-responsive cargo release significantly enhanced the abilities of gefitinib-loaded GO nanosheets to induce cell apoptosis, suppress cell proliferation, and inhibit tumor growth in lung cancer cell-bearing mice.
Conclusion: The results demonstrated the potential utility of NGO-SS-HA-Gef for therapeutic applications in the treatment of lung cancer.

Keywords: nano-graphene oxide, gefitinib, hyaluronic acid, CD44, redox-responsive

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