Functionalized Graphene Platforms for Anticancer Drug Delivery

Abstract

Two-dimensional nanomaterials are emerging as promising candidates for a wide range of biomedical applications including tissue engineering, biosensing, pathogen incapacitation, wound healing, and gene and drug delivery. Graphene, due to its high surface area, photothermal property, high loading capacity, and efficient cellular uptake, is at the forefront of these materials and plays a key role in this multidisciplinary research field. Poor water dispersibility and low functionality of graphene, however, hamper its hybridization into new nanostructures for future nanomedicine. Functionalization of graphene, either by covalent or non-covalent methods, is the most useful strategy to improve its dispersion in water and functionality as well as processability into new materials and devices. In this review, recent advances in functionalization of graphene derivatives by different (macro)molecules for future biomedical applications are reported and explained. In particular, hydrophilic functionalization of graphene and graphene oxide (GO) to improve their water dispersibility and physicochemical properties is discussed. We have focused on the anticancer drug delivery of polyfunctional graphene sheets.

Keywords: anticancer drug delivery; functionalization; graphene; photothermal therapy; two-dimensional nanomaterials.

Figure 1

Graphite and different allotropic forms of carbon.

Figure 2

Structure of graphene and its oxidized derivatives.

Figure 3

The controlled functionalization of nanographene sheets through nitrene [2+1] cycloaddition reaction at ambient conditions.

Figure 4

GO with PEI coverage coloaded with cisplatin and topotecan for mitochondria targeting of cancer cells.

Figure 5

Schematic representation of the synthesis and cellular uptake of GO nanoparticle/chitosan hybrids as drug delivery system.

Figure 6

(A) The chemical structure of the polyglycerol-covered nanographene with the mitochondria-targeting ligands and charge conversional functional groups. (B) Multifunctional drug delivery system accumulates in mitochondria by targeting ligands and photothermal properties under NIR laser irradiation result in drug release and good therapeutic efficiency.

Figure 7

Functionalized rGO with thiol-maleimide containing catechol (dopa-MAL) as a targeted drug delivery system for DOX to destroy human breast adenocarcinoma cancer cells (MDA-MB-231).

Figure 8

Synthesis of folic acid-functionalized PEGylated GO (GO-PEG-Fol), with small size and narrow size distribution (∼30 ± 5 nm), and the ability of efficient converting NIR light into heat.

Figure 9

(A) Schematic representation of the synthesis of the polyglycerol amine functionalized graphene sheets (GA), polyglycerol sulfate-functionalized graphene sheets (GS) and conjugation of pH-sensitive dye to the GA and GS (GAD, GSD). Information regarding the synthesis these graphene platforms can be found in ref. In vitro release profile of DOX from the GAD (B) and GSD (C) at 37 °C in various media.

Figure 10

Schematic presentation of the functionalization of QDs by poly(l-lactide)-PEG and their application for cell imaging.

Figure 11

Schematic representation of the synthesis of DOX-BSA-rGO as a light sensitive drug delivery system for chemo-photothermal therapy.

Figure 12

Schematic presentation of fabrication of GO-based gene delivery system through covalent attachment of LMW BPEI to this platform.