Abstract
The use of graphene to target and eliminate cancer stem cells (CSCs) is an alternative approach to conventional chemotherapy. We show the biomolecule-mediated synthesis of reduced graphene oxide–silver nanoparticle nanocomposites (rGO–Ag) using R-phycoerythrin (RPE); the resulting RPE–rGO–Ag was evaluated in human ovarian cancer cells and ovarian cancer stem cells (OvCSCs). The synthesized RPE–rGO–Ag nanocomposite (referred to as rGO–Ag) was characterized using various analytical techniques. rGO–Ag showed significant toxicity towards both ovarian cancer cells and OvCSCs. After 3 weeks of incubating OvCSCs with rGO–Ag, the number of A2780 and ALDH+CD133+ colonies was significantly reduced. rGO–Ag was toxic to OvCSCs and reduced cell viability by mediating the generation of reactive oxygen species, leakage of lactate dehydrogenase, reduced mitochondrial membrane potential, and enhanced expression of apoptotic genes, leading to mitochondrial dysfunction and possibly triggering apoptosis. rGO–Ag showed significant cytotoxic potential towards highly tumorigenic ALDH+CD133+ cells. The combination of rGO–Ag and salinomycin induced 5-fold higher levels of apoptosis than each treatment alone. A combination of rGO–Ag and salinomycin at very low concentrations may be suitable for selectively killing OvCSCs and sensitizing tumor cells. rGO–Ag may be a novel nano-therapeutic molecule for specific targeting of highly tumorigenic ALDH+CD133+ cells and eliminating CSCs. This study highlights the potential for targeted therapy of tumor-initiating cells.
Highlights
Ovarian cancer is the sixth most common malignancy and fifth most common disease in women worldwide
We explored the possibility of using RPE to reduce graphene oxide and synthesize reduced GO (rGO)–Ag
The cytotoxic potential of RPE-mediated synthesis of rGO–Ag was evaluated in ovarian cancer cells and different subpopulations of ovarian cancer stem cells (OvCSCs) using various cellular assays
Summary
Ovarian cancer is the sixth most common malignancy and fifth most common disease in women worldwide. The standard therapy management generally involves a combination of surgical tumor debulking and chemotherapy [5]. Over the past few decades, combination therapy and chemotherapy have been the standard treatments and involve a combination of intravenous platinum and taxane chemotherapy for advanced cancer [6]. Numerous molecular targeting agents are available, the standard combination of surgery and chemotherapy for treating ovarian cancer results in recurrence in 70% of patients who undergo the first-line treatment within 18 months [1,7]. Ovarian cancer cells comprise a heterogeneous population of cells with distinct properties and functions. Some of these cells exhibit increased tumorigenicity and differentiating capacity and are called CSCs [9,10]
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