Original ArticleSpecial Topic: Two-Dimensional Biomaterials in Regenerative Medicine
Formation of graphene oxide-hybridized nanogels for combinative anticancer therapy

https://doi.org/10.1016/j.nano.2017.05.007Get rights and content

Abstract

The low efficacy and high toxicity of chemotherapy have been driving increasing attention on development of combined anticancer therapy technique. In the current work, graphene oxide (GO)-hybridized nanogels (AGD) were developed for delivery of an anticancer drug (doxorubicin (DOX)), which simultaneously presented photothermal therapeutic effects against cancer cells. AGD nanogels were fabricated by in situ incorporating GO nanoplatelets into a biodegradable polymer (alginate) via a double emulsion approach using a disulfide molecule as crosslinker, followed by DOX encapsulation via electrostatic interactions. The nanogels released DOX drug in an accelerated way under both acidic and reducible conditions mimicking extracellular tumor microenvironments and intracellular compartments. The stimulative release controllability of the nanogels improved the DOX internalization and long-term drug accumulation inside A549 cells (an adenocarcinoma human alveolar basal epithelial cell line), which, together with their photothermal effect, resulted in a good anticancer cytotoxicity, indicating their promising potential for combinative anticancer therapy.

Graphical Abstract

2D graphene oxide-hybridized nanogels enable a pH/redox-dual sensitivity in anticancer delivery, which, together with their photothermal effect, offers a combined therapy technique for anticancer treatment.

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Section snippets

Materials and cells

Alginate acid sodium salt (from brown algae, Mw from 12 to 58 kDa, cell culture tested) (Alg), polyvinyl alcohol (PVA, Mw 89–98 kDa), and glutathione (GSH) were bought from Sigma, China. Cystamine dihydrochloride was purchased from Shanghai Hansi Chemical Co. Ltd., China. 1-Ethyl-3-(3-dimethylamino propyl) carbodiiamide hydrochloride (EDC) was purchased from Shanghai Yuan Ju Biological Technology Co., Ltd., China. Dioctyl sodium sulfosuccinate (AOT) was obtained from Aladdin Co. Ltd., China.

Development and physical properties of GO-hybridized nanogels

Graphene oxide (GO) for this study was prepared from natural graphite product using a Hummers method, followed by sonication to break them into proper small nanoplatelets.37, 38 The obtained GO samples assume as a two dimensional (2D) nanostructure (50-150 nm wide and ~5 nm thick) by atomic force microscope (AFM) observation (Figure 2). GO-hybridized nanogels were developed using a double emulsion method (Figure 1). The carboxylic groups on alginate and GO were firstly activated by

Discussion

Successful treatment of cancers by a single thermotherapeutic method is still limited by the low anticancer efficacy and high toxicity of small anticancer chemical molecules associated with multidrug resistance.3, 4, 5, 6, 7, 8, 9, 10, 11 The current nanomedicines (DOXil and Abraxane®) which have been clinically employed have not yet solved the low anticancer bioactivity due to their uncontrollable structure as well as their passive drug release properties.12, 13, 14 In this study, graphene

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    Financial support: This research was supported by Shanghai International Cooperation Program (15520721200) and Shanghai Municipal Natural Science Foundation (15ZR1408500). We also acknowledged the financial support from Fundamental Research Funds for the Central Universities (WD1714002, WD1717015).

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