Differentiation of Cancer Stem Cells through Nanoparticle Surface Engineering
Yingying Geng, John J. Amante, Hira Lal Goel, Xianzhi Zhang, Melanie R. Walker, David C. Luther, Arthur M. Mercurio, Vincent M. Rotello
Abstract
Cancer stem cells (CSCs) are a crucial therapeutic target because of their role in resistance to chemo- and radiation therapy, metastasis, and tumor recurrence. Differentiation therapy presents a potential strategy for "defanging" CSCs. To date, only a limited number of small-molecule and nanomaterial-based differentiating agents have been identified. We report here the integrated use of nanoparticle engineering and hypothesis-free sensing to identify nanoparticles capable of efficient differentiation of CSCs into non-CSC phenotypes. Using this strategy, we identified a nanoparticle that induces CSC differentiation by increasing intracellular reactive oxygen species levels. Importantly, this unreported phenotype is more susceptible to drug treatment than either CSCs or non-CSCs, demonstrating a potentially powerful strategy for anticancer therapeutics.