The combination of chemotherapy and photodynamic therapy has emerged as a promising strategy for cancer therapy due to its synergistic effects. In this work, PEGylated silver nanoparticles decorated with graphene quantum dots (Ag-GQDs) were tested as a platform to deliver a chemotherapy drug and a photosensitizer, simultaneously, in chemo-photodynamic therapy against HeLa and DU145 cancer cells in vitro. Ag-GQDs have displayed high efficiency in delivering doxorubicin as a model chemotherapy drug to both cancer cells. The Ag-GQDs exhibited a strong antitumor activity by inducing apoptosis in cancer cells without affecting the viability of normal cells. Moreover, the Ag-GQDs exhibited a cytotoxic effect due to the generation of the reactive singlet oxygen upon 425 nm irradiation, indicating their applicability in photodynamic therapy. In comparison with chemo or photodynamic treatment alone, the combined treatment of Ag-GQDs conjugated with doxorubicin under irradiation with a 425 nm lamp significantly increased the death in DU145 and HeLa. This study suggests Ag-GQDs as a multifunctional and efficient therapeutic system for chemo-photodynamic modalities in cancer therapy.

Tumor microenvironment complexity render chemotherapy and radiotherapy ineffective to eradicate highly aggressive tumors. For this reason, we are interested to find new avenues that can improve clinical outcomes. Recently, different nanomaterials such as Graphene Quantum Dots (GQDs) have been explored in treatments for a broad range of diseases, including cancer therapeutics. GQDs are nanometer-sized fragments (2-20 nm) of graphene, which have shown unique electrical, optical and mechanical properties. We hypothesize that the unique physical and chemical properties of the Graphene Quantum Dots (GQDs) along with the anticancer properties of silver (Ag) can provide an alternative to the challenges presently encountered in traditional cancer therapy regimens. In this study functionalized silver decorated graphene quantum dots (Ag-GQDs) nanocomposites were synthesized by a bottom-up approach by the pulsed laser irradiation of a liquid hydrocarbon precursor containing silver ions. The Ag-GQDs were characterized by UV-Vis spectroscopy, transmission electron microscopy, and Fourier transform IR spectroscopy. The Ag-GQD nanocomposites were tested in the treatment of cervical cancer HeLa cells and prostate cancer cells DU-145. The Ag-GQD nanocomposites demonstrated high potential in the delivery of Doxorubicin to cancer cells and an anticancer activity boost due to their intrinsic properties. Interestingly, we observed an increase in the activity of caspase-3/7 in DU145 and HeLa when treated with such nanoparticles. The photo-activation of Ag-GQDs with 425 nm radiation increased the levels of Reactive Oxygen Species (ROS) in both cell lines, inducing cell death by DNA damage. The combination of the chemo-photodynamic therapies using Ag-GQDs conjugated with DOX remarkably enhanced the treatment efficacy of HeLa and DU145, as compared to treatment by using each modality alone. HeLa. Fluorescence imaging results showed that Ag-GQDs deliver DOX to the nucleus of cancer cells, which suggests they may deliver other cargos. Also, to confirm whether the decrease in the cells viability upon treatment with Ag-GQDs was caused by toxicity, we tested a non-transformed cell line. The data suggest that the effect is due to the intrinsic effect of Ag-GQDs and not by toxicity. The Ag-GQDs thus offer a general platform for incorporating multiple therapeutic modalities for treating different types of cancer and they represent a significant breakthrough in nanomedicine for potential translation to the clinic. Further studies are necessary to elucidate the exact mechanism(s) of Ag-GQDs in releasing their cargo, and to test them in vivo. In summary, we developed a novel, multi-functional, and biocompatible PEGylated Ag-GQDs nanocomposites that combines two therapeutic modalities, chemotherapy and photodynamic therapy, into one platform for treatment of different type of cancers. Citation Format: Joel Encarnación-Rosado, Khaled Habiba, Kenny García-Pabón, Brad R. Weiner, Gerardo Morell. Improving cytotoxicity against cancer cells by chemo-photodynamics combined modalities using silver/graphene quantum dots/doxorubicin nanoconjugates. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2196.