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Nanoparticles and Cancer Stem Cells
Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug clearance. Antibodies and ligands targeting the unique factors that maintain the niche are utilized for the delivery of anticancer therapeutics to CSCs. In this regard, nanomaterials, specifically nanoparticles (NPs), are extremely useful as carriers for the delivery of anticancer agents to CSCs.
Self-renewal and DNA repair: this extraordinary property of CSCs causes tumor relapse and radiation-resistance in tumors .
Differentiation into multiple cell types: the pluripotency of CSCs causes heterogeneity in solid tumors .
Ionizing radiation: this feature makes CSCs resistant to radiotherapy.
Infinite proliferative potential: unlimited cell division, which leads to rapid tumor growth.
Dormancy state: CSCs enter dormancy to evade the attack by the immune system, awaiting new signals from the environment to re-enter the cell cycle .
Elevated expression of ATP-binding cassette (ABC) pumps and detoxifying enzymes to increase the drug’s efflux, which is considered to be an important mechanism for multi-drug resistance (MDR). Multi-drug resistance is either intrinsic and present before the start of treatment or acquired after exposure to treatment .
The stochastic or classical model states that any somatic cell has the intrinsic ability to undergo mutation and transform into CSCs driven by genetic instability or environmental signals, as shown in Figure 1A;
2. Self-Assembling Protein NPs
Naturally occurring or synthetic amino acid sequences used in assembling protein NPs can be immunogenic. The immune response can neutralize the drug’s effectiveness or cause serious side effects in therapeutic applications. In some cases, these peptides can be immunosuppressive, and their long-term administration can cause severe side effects, such as relapsed bacterial, viral, or fungal infections . The targeting agent in the delivery of cytotoxic proteins should have a high selectivity for receptors on tumor-associated cells to reduce the risk of serious side effects in healthy tissues .
The entry is from 10.3390/nano11071755
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