Differentiation of Cancer Stem Cells through Nanoparticle Surface Engineering

• Published in: ACS nano Vol. 14; no. 11; pp. 15276 - 15285
• Main Authors: Geng, Yingying, Amante, John J, Goel, Hira L, Zhang, Xianzhi, Walker, Melanie R, Luther, David C, Mercurio, Arthur M, Rotello, Vincent M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 24.11.2020
• Subjects: Antineoplastic Agents; Cell Differentiation; Humans; Nanoparticles; Neoplasms; Neoplastic Stem Cells; array-based sensing; phenotype; nanoparticle surface engineering; breast cancer; cancer stem cell; differentiation therapy
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.0c05589

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.