Multi-Functionalised Nano-Graphene Oxide Nanocarriers in Controlled Release & Drug Delivery

2-D graphene provides outstanding properties that are currently being studied. These outstanding properties include:

• Electronic properties; 
• Thermal properties; 
• Mechanical properties. 

For example, 2-D graphene is currently being explored in the following applications (among many other applications):

• Advanced nanoelectronics; 
• Nanomembranes; 
• Nanocomposites. 

In this article, I will discuss some of the applications of nano-graphene oxide in nanomedicine.

Nano-graphene oxide (NGO) is a single-layer of graphene oxide sheets with a lateral width of a few nanometres.

The Journal of Materials Chemistry published on 19 Nov 2010 a work titled "Multi-functionalized graphene oxide based anticancer drug-carrier with dual-targeting function and pH-sensitivity". Scientists from P. R. China designed a nano-graphene oxide (NGO) anticancer drug nanocarrier that combines different targeting mechanisms.

Many anti-cancer drugs are toxic and/or cause undesirable side-effects. This is due to the fact that these anti-cancer drugs:

• Target tumour cells; 
• And also target healthy cells. 

A team of scientists leaded by Yongsheng Chen (from Nankai University, P. R. China) have developed a controlled release system using multi-functionalised NGO as a drug nanocarrier for drug delivery.

The team headed by Chen selected NGO to build up the drug nanocarrier because this nanomaterial has a very high surface area available. Thus, NGO presents high ability to carry a large amount of drug, thereby contributing to a more efficient therapy and with increased yield, on the standpoint of dosage.

The NGO was multi-functionalized in order to become targeted. For this purpose, the Chen's team used several approaches:

• The team headed by Chen linked super-paramagnetic Fe3O4 nanoparticles to the NGO nanocarrier. By proceeding this way, the NGO nanocarrier became targeted to the tumour cells by an external magnetic field;
• Many cancer cells have a high number of folate receptors on their external cellular surface. As a consequence of this fact, folic acid is a targeting agent of some (not all) tumour cells. Therefore, the Chen's team attached folic acid to the nanoparticles. More precisely, the Chen's team conjugated folic acid onto Fe3O4 nanoparticles via the chemical linkage with amino groups of the 3-aminopropyl triethoxysilane (APS) modified superparamagnetic NGO–Fe3O4 nanohybrid, in order to generate the multi-functionalized NGO. This procedure made the NGO nanocarrier more likely that the drug nanocarrier will enter cancer cells rather than healthy cells;
• Cancer cells are typically more acidic than healthy cells. Therefore, the Chen's team developed the NGO nanocarrier with the ability to increase drug release when the pH value of the surrounding environment decreases. This mechanism warrants that the drug is released to the tumour cells, minimizing this way the uptake of anti-cancer drug by healthy cells.

After multi-functionalization process, the NGO nanocarriers were then loaded (via π–π stacking or pi-pi stacking) onto the surface of this multi-functionalized NGO with a strong anti-cancer drug: Doxorubicin Hydrochloride (Dox).

Cell uptake studies were carried out the Chen's team, using fluorescein isothiocyanate labelled or Dox loaded multi-functionalized NGO drug nanocarrier to evaluate:

• Their targeted delivery property; 
• Toxicity to tumour cells. 

These studies focused on cell uptake and toxicity were carried out in human breast cancer cells in vitro. The results show that this multi-functionalized NGO drug nanocarrier has potential applications for targeted delivery and the controlled release of anticancer drugs.

Obviously this scientific breakthrough needs further studies aiming improvement in what concerns toxicology, biodegradability and passing from the in vitro studies to humans. Anyway, this discovery has intrinsic value and may pave the way for progress in nanotechnology in drug delivery.

This scientific breakthrough is relevant due to the following reasons:

• Progress was achieved in the improvement of targeting of nanocarriers against cancer cells; 
• The effectiveness of treatments is improved, since practically all the anti-cancer drug is delivered to cancer cells; 
• The undesirable side-effects for patients are significantly reduced; 
• Progress was achieved in the applications of graphene (in this case, graphene oxide) in controlled release and nanotechnology in drug delivery. 

For further information, I suggest to readers the following links (which served as the basis for this article):

http://www.rsc.org/Publishing/ChemScience/Volume/2010/12/targeting_tumours.asp

http://pubs.rsc.org/en/Content/ArticleLanding/2011/JM/c0jm02494e