Functionalization of Reduced Graphene Oxide via Thiol–Maleimide “Click” Chemistry: Facile Fabrication of Targeted Drug Delivery Vehicles

Abstract

Materials based on reduced graphene oxide (rGO) have shown to be amenable to noncovalent functionalization through hydrophobic interactions. The scaffold, however, does not provide sufficient covalent linkage given the low number of reactive carboxyl and alcohol groups typically available on the rGO. The integration of clickable groups, particularly the ones that can undergo efficient conjugation without any metal catalyst, would allow facile functionalization of these materials. This study reports on the noncovalent association of a maleimide-containing catechol (dopa-MAL) surface anchor onto the rGO. Thiol-maleimide chemistry allows thereafter the facile attachment of thiol-containing molecules under ambient metal-free conditions. Although the attachment of glutathione and 6-(ferrocenyl)hexanethiol was used as model thiols, the attachment of a cancer cell targeting cyclic peptide, c(RGDfC), opened the possibility of using the dopa-MAL-modified rGO as a targeted drug delivery system for doxorubicin (DOX). Although free DOX showed to be more effective at killing the human cervical cancer cells (HeLa) over human breast adenocarcinoma cancer cells (MDA-MB-231), the DOX-loaded rGO/dopa-MAL-c (RGDfC) nanostructure showed an opposite effect being notably more effective at targeting and killing the MDA-MB-231 cells. The effect is enhanced upon laser irradiation for 10 min at 2 W cm. The facile fabrication and functionalization to readily obtain a functional material in a modular fashion make this clickable-rGO construct an attractive platform for various applications.

A Facile Route to Fabricate CS/GO Composite Film for the Application of Therapeutic Contact Lenses

“…Moreover, some charged polysaccharides such as chitosan, hyaluronic acid, and chondroitin sulfate could have interactions with oppositely charged drug molecules, which could also help to control drug loading and releasing [5,18]. Additionally, graphene family materials have a conjugated structure, which can absorb drug molecule through π-π interactions [18,[23][24][25][26][27][28]. Moreover, the oxygen permeability of CS film had been confirmed by previous research [29].…”

Functionalized Reduced Graphene Oxide as a Versatile Tool for Cancer Therapy

“…Using thiol-maleimide chemistry, they modify rGO with cyclic peptide c(RGDfC) as a targeting ligand for targeted delivery of DOX to cancer cells. The in vitro studies performed with MDA-MB-231 cell line indicated that DOX loaded rGO/dopa-MAL-c(RGDFC) was more effective than free DOX in killing the cancer cells after exposure to 980 nm laser irradiation (2 W/cm 2 ) for 10 min [117]. This was attributed to the enhancement of chemotherapy with PTT from the endocytosed nanocomposite upon NIR laser exposure for targeted synergistic cancer cell killing.…”

Graphene and its derivatives: understanding the main chemical and medicinal chemistry roles for biomedical applications

“…Oz et al reported the noncovalent association of a maleimide-catechol compound (DOPA-MAL) with rGO from π – π interactions and hydrogen bonds. This nanosystem has been associated with doxorubicin (DOX) to evaluate the treatment of cervical cancer (HeLa) and breast cancer (MDA-MB-231) [ 169 ].…”