Exceedingly biocompatible and thin-layered reduced graphene oxide nanosheets and its application in co-delivery of curcumin and paclitaxel shows highly potent synergistic anticancer effects in A549 and MDA-MB-231 cells

Muthoosamy, Kasturi (2016) Exceedingly biocompatible and thin-layered reduced graphene oxide nanosheets and its application in co-delivery of curcumin and paclitaxel shows highly potent synergistic anticancer effects in A549 and MDA-MB-231 cells. PhD thesis, University of Nottingham.

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Abstract

Delivery of anti-cancer drugs using graphene and its derivatives: graphene oxide (GO) and reduced graphene oxide (RGO) has sparked major interest in this emerging field. The anti-cancer therapies often pose a limitation of insolubility, administration problems and cell-penetration ability. In addition, systemic toxicity caused by lack of selective targeting towards cancer cells and inefficient distribution limits its clinical applications. Graphene nanocomposite is a promising tool to address these drawbacks. Graphene is a flat monolayer of carbon atoms that holds many promising properties such as unparalleled thermal conductivity, remarkable electronic properties, and most intriguingly high planar surface and superlative mechanical strength, which are attractive in biotechnology applications.

However the synthesis route for the production of GO or RGO often involves the use of harsh chemicals which jeopardize its further application as a drug delivery cargo. To overcome these limitations, a simple one-pot strategy was used to synthesize RGO nanosheets by utilizing an easily available over-the-counter medicinal and edible mushroom, Ganoderma lucidum. The produced RGO was readily dispersible in water and various solvents. The RGO was highly biocompatible towards colon (HT-29), brain (U87MG) and normal cells (MRC-5). By functionalization of RGO with an amphiphilic polymer, PF-127, a more stable RGO was produced, called GP. Curcumin (Cur) and Paclitaxel (Ptx) was then loaded onto the GP cargo, resulting in a nano-sized GP-Cur-Ptx sytem with the particle size of 140 nm. A remarkably high drug loading was also achieved with 678 wt.%, highest thus far, compared to any other Cur nanoformulations. Based on cell proliferation assay, the GP-Cur-Ptx is a synergistic treatment and is highly potent towards A549 (lung) and MDA-MB-231 (breast) cancer cells. These positive findings are further confirmed by increased reactive oxygen species (ROS); mitochondrial membrane potential (MMP) depletion; and cell apoptosis. The same treated with normal cells (MRC-5) shows that the system is biocompatible and cell-specific.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Manickam, Sivakumar
Keywords: reduced graphene oxide, synergistic treatment, A549, MDA-MB-231, curcumin
Subjects: T Technology > TP Chemical technology
Faculties/Schools: UNMC Malaysia Campus > Faculty of Engineering > Department of Chemical and Environmental Engineering
Item ID: 34368
Depositing User: MUTHOOSAMY, KASTURI
Date Deposited: 26 Jan 2018 06:04
Last Modified: 28 Jan 2018 05:18
URI: http://eprints.nottingham.ac.uk/id/eprint/34368

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