Water-soluble carbon dots (C-dots) were prepared through microwave-assisted pyrolysis of an aqueous solution of dextrin in the presence of sulfuric acid. The C-dots produced showed multicolor luminescence in the entire visible range, without adding any surface-passivating agent. X-ray diffraction and Fourier transform infrared spectroscopy studies revealed the graphitic nature of the carbon and the presence of hydrophilic groups on the surface, respectively. The formation of uniformly distributed C-dots and their luminescent properties were, respectively, revealed from transmission electron microscopy and confocal laser scanning microscopy. The biocompatible nature of C-dots was confirmed by a cytotoxicity assay on MDA-MB-468 cells and their cellular uptake was assessed through a localization study.

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Akt overexpression in cancer causes resistance to traditional chemotherapeutics. Silencing Akt through siRNA provides new therapeutic options; however, poor in vivo siRNA pharmacokinetics impede translation. We demonstrate that acidic milieu-sensitive multilamellar gold niosomes (Nio-Au) permit targeted delivery of both Akt-siRNA and thymoquinone (TQ) in tamoxifen-resistant and Akt-overexpressing MCF7 breast cancer cells. Octadecylamine groups of functionalized gold nanoparticles impart cationic attribute to niosomes, stabilized through polyethylene glycol. TQ's aqueous insolubility renders its encapsulation within hydrophobic core, and negatively charged siRNA binds in hydrophilic region of cationic niosomes. These niosomes were exploited to effectively knockdown Akt, thereby sensitizing cells to TQ. Immunoblot studies revealed enhanced apoptosis by inducing p53 and inhibiting MDM2 expression, which was consistent with in vivo xenograft studies. This innovative strategy, using Nio-Au to simultaneously deliver siRNA (devoid of any chemical modification) and therapeutic drug, provides an efficacious approach for treating therapy-resistant cancers with significant translational potential.

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