Cancer Therapy Using Ultrahigh Hydrophobic Drug-Loaded Graphene Derivatives (original) (raw)

This study aimed to demonstrate that curcumin (Cur)-containing graphene composites have high anticancer activity. Specifically, graphene-derivatives were used as nanovectors for the delivery of the hydrophobic anticancer drug Cur based on pH dependence. Different Cur-graphene composites were prepared based on polar interactions between Cur and the number of oxygen-containing functional groups of respective starting materials. The degree of drug-loading was found to be increased by increasing the number of oxygen-containing functional groups in graphene-derivatives. We demonstrated a synergistic effect of Cur-graphene composites on cancer cell death (HCT 116) both in vitro and in vivo. As-prepared graphene quantum dot (GQD)-Cur composites contained the highest amount of Cur nano-particles and exhibited the best anticancer activity compared to the other composites including Cur alone at the same dose. This is the first example of synergistic chemotherapy using GQD-Cur composites simultaneous with superficial bioprobes for tumor imaging. W ith the recent rapid progress in nano-biotechnology, the use of nanomaterials as drug carriers for cancer therapy is receiving increased attention 1,2. Carbon nanostructures (e.g., graphene-derivatives and graphene quantum dots (GQDs)) exhibit favourable biocompatibility with low toxicity, excellent physical properties, a surface amenable to modification, improved multifunctionality, and compatibility with conventional graphene technology 2,3. In particular, the use of graphene-derivatives is very promising for a wide range of biological applications, including the recent development of GQD-based bioprobes for tumor imaging 4,5. However, existing drug carriers including proteins, amphiphilic block copolymers, lipids, and inorganic nanoassemblies are associated with a number of drawbacks including undesirable burst drug release and premature drug leakage due to limited stability 6,7. It was recently demonstrated that graphene materials can be loaded with aromatic ring-containing anticancer drugs such as doxorubicin (DOX) and camptothecin (CPT) with ultrahigh efficiency 3,8-12. Graphene-oxide-derivative-Cur composites have also been reported to have anticancer activity 13,14 , but they are neither very effective nor easily produced. Indeed, their use has not been demonstrated in a real application, i.e., treating tumours or inhibition of tumor growth, and their drug-loading capability is low, suggesting that they are not ideal for clinical applications. There have also been reports of graphene quantum dotloaded drugs, but they are not efficient and have not been shown to be useful for any real applications such as tumor treatment 15,16. The use of graphene-based nanomaterials deserves attention in order to overcome this physiological barrier because these nanomaterials exhibit excellent adsorption properties in the bloodstream 17-19. Therefore, graphene-based drug delivery nanosystems that are compatible with physiological environments are very desirable. As a result, the use of graphene in biomedicine is being investigated 20,21. Of particular interest, recent studies have shown that graphene-derivatives exhibit excellent catalytic performance owing to the high surface area for producing polar interactions with oxygen-containing functional groups, which is also a significant factor for the enhancement of drug-loading capacity 3,9,22. In the search for pharmaceutical agents for the treatment of cancer, many different hydrophobic drugs such as Cur have been found to be highly effective against various carcinomas. However, the low solubility of these hydrophobic drugs in aqueous media hinders their clinical use for the treatment of cancer.