A graphene oxide anticancer drug carrier that combines different targeting mechanisms has been designed by scientists from China.
Many anticancer drugs are toxic or cause harmful side effects because they target healthy cells as well as tumour cells. Yongsheng Chen from Nankai University, China, and colleagues have developed a delivery system using functionalised graphene oxide as the drug carrier. Graphene oxide has a very high surface area, enabling it to transport a large amount of the drug. As cancer cells are typically more acidic than normal cells, the team developed the system to increase drug release as pH decreases. This confines the drug to the tumour site and limits uptake by healthy cells. This could allow doctors to use higher doses and improve the effectiveness of treatments, or reduce side-effects for patients.
Chen's team attached superparamagnetic Fe3O4 nanoparticles to the graphene oxide. 'Using Fe3O4 nanoparticles linked to the graphene oxide allows the carrier to be targeted to the tumour site by an external magnetic field,' explains Chen. Many cancer cells have high numbers of folate receptors on their surface so the team attached folic acid to the nanoparticles as a second targeting mechanism. This makes it more likely that the drug carrier will enter tumour cells rather than healthy cells. The team then loaded doxorubicin, a potent anticancer drug, onto the graphene oxide via pi-pi stacking.
Preparation of the multi-functionalised graphene oxide anticancer drug carrier
They tested the carrier in cell uptake and toxicity studies in human breast cancer cells in vitro. These tests confirmed that the carrier can transport and release doxorubicin into tumour cells.
Michael Sailor, an expert in designing nanoparticles for biomedical applications at the University of California, San Diego, US, cautions that further work is needed to test the safety and biological life cycle of any graphene-based drug delivery system. 'One of the major challenges in nano-enabled drug delivery is degradability of the device once it has performed its function. Although many nanoparticles are safely excreted by the body, many others are not. Future patients will be concerned about a nanodevice sticking around after it has delivered its drug or performed its diagnostic test.'
'Nanomaterial-based targeting drug delivery systems are still at an early stage for commercial applications,' agrees Chen. 'Some reports suggest that modified graphene can be excreted safely from the body, but the digestion or downgrading of nano-delivery vehicles needs more research. This is the focus of our future studies.'
Russell Johnson
RSC
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