Targeting Cancer Stem Cells and Non-Stem Cancer Cells: The Potential of Lipid- Based Nanoparticles

Background: Cancer stem cells (CSCs) have been described as a relevant contributor to tumorigenicity, metastasis, tumor recurrence and drug resistance, making this cell population a relevant target in solid tumors. Methods: This has stimulated the development of different therapeutic strategies often targeting surface markers (CD44, epithelial cell adhesion molecule (EpCAM), aldehyde dehydrogenase (ALDH) and nucleolin) and/or signaling pathways that are aberrantly activated and contribute to CSCs proliferation and survival. Results: There are a variety of signaling pathways often involved in physiological processes of cell function that aberrantly regulate CSCs, including Notch, Hedgehog, Wnt, PI3K/Akt, JAK/STAT and Ras/ERK signaling pathways. The inhibition of these pathways usually depletes CSC population and increases tumor sensitivity to chemotherapy. However, the recognition of the potential of cells to interconvert in response to environmental stimulus, turned both CSCs and non-stem cancer cells into two relevant therapeutic targets. Therefore, the use of drug combinations is increasingly needed. These drugs with different mechanisms of action often characterized by distinct pharmacokinetics profiles and, as such, will present distinct biodistribution patterns, following systemic administration. To synchronize pharmacokinetics, one can encapsulate synergistic drug combinations into lipidbased nanoparticles, assuring tumor delivery of the selected drug ratio. Conclusion: This review will focus on the multiple strategies to target CSCs, as well as on the potential of lipidbased nanoparticles to target both CSCs and non-stem cancer cells