Targeted delivery and controlled release of doxorubicin into cancer cells using a multifunctional graphene oxide

• Published in: Materials Science & Engineering C 2016-02, Vol.59, p.652-660
• Main Authors: Lv, Yao, Tao, Lei, Annie Bligh, S.W., Yang, Huihui, Pan, Qixia, Zhu, Limin
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Cancer; Carriers; Cell Line, Tumor; Cell Survival - drug effects; Controlled release; Disaccharides - chemistry; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacokinetics; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drugs; Functionalised graphene oxide; Graphene; Graphite - chemistry; Hepatocellular carcinoma; Humans; Lactobionic acid; Oxides; PEG linker; pH responsive; Polyetherimides; Polyethylene Glycols - chemistry
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2015.10.065

We have synthesized a new multifunctional graphene oxide as a drug carrier targeting to hepatocarcinoma cells. Surface modified graphene oxide with polyethyleneimine (PEI) sequentially derivatised with fluorescein isothiocyanate (FI) and polyethylene glycol (PEG)-linked lactobionic acid (LA), and acetylation of remaining terminal amines of the PEI produced a new multifunctional graphene oxide drug carrier (GO/PEI.Ac-FI-PEG-LA). Doxorubicin (DOX), an anticancer drug, was encapsulated in GO/PEI.Ac-FI-PEG-LA to give GO/PEI.Ac-FI-PEG-LA/DOX, with a drug loading percentage of 85%. We showed that both GO/PEI.Ac-FI-PEG-LA and GO/PEI.Ac-FI-PEG-LA/DOX were water soluble and stable between pH 5.0 and 9.0. In vitro release studies indicated that the release rate of DOX from GO/PEI.Ac-FI-PEG-LA/DOX complexes were significantly higher at pH5.8 than that of the physiological pH. Another important feature of this carrier is its good cell viability in the tested concentration range (0‐4μM), and the GO/PEI.Ac-FI-PEG-LA/DOX can specifically target cancer cells overexpressing asialoglycoprotein (ASGPR) receptors and exert growth inhibition effect to the cancer cells. The enhanced target specificity and the substantial improvement in pH responsive controlled release have made this new carrier a potential choice for non-covalent encapsulation of drugs in GO, and a delivery system for cancer therapy. [Display omitted] •Graphene oxide with functionalized modification for cancer drug delivery•High drug loading capacity•pH-responsive drug release behavior•Specifically target delivery and effectively cell inhibition