Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 13, Issue -, Pages 7457-7472Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S173889
Keywords
nano-graphene oxide; gefitinib; hyaluronic acid; CD44; redox-responsive
Funding
- Ministry of Science and Technology of China [2015CB931804]
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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.
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