Using Self-Assembled Nanomaterials to Inhibit the Formation of Metastatic Cancer Stem Cell Colonies in Vitro

Abstract

The isolation of cells with stem-like properties from prostate tumors suggests the presence of a cancer stem cell (CSC) population, which may account for the initiation, progression, and metastasis as well as drug resistance of the disease. We hypothesized that containing, or at least immobilizing, the CSCs in a nanoself-assembling material might help prevent prostate tumor progression or metastasis. CSCs were plated in three conditions: 1) placed in 1% concentration self-assembled peptide (SAP) preequilibrate with culture medium; 2) placed in 3% concentration SAP preequilibrate with culture medium; and 3) in nonadherent culture. All were grown for 14 days, after which the cells in both 1% and 3% concentrations were washed out of the SAP and grown for an additional 14 days. Here we report that CSCs from prostate cancer cell lines remained quiescent for more than 28 days when embedded in SAP. When the prostate CSCs were embedded in 1% and 3% SAP, most of the CSCs remained single cells 14 days after plating in a nonadherent plate; no prostaspheres could be detected 14 days after plating, suggesting that self-renewal was significantly suppressed. In the controls, prostate CSCs began to divide 1 day after plating in a nonadherent plate and prostaspheres were visible at day 10, indicating the active self-renewal property of the prostate CSCs. Our findings suggest that SAP can completely inhibit a prostate CSC from self-renewal while preserving its viability and CSC property. Therefore, SAP may be an effective nanomaterial for inhibiting cancer progression and metastasis to stop the progression during treatment and removal.

Design of Self-Assembling Peptides and Their Biomedical Applications

“…In a recent study, Ellis-Behnke and coworkers have reported that self-assembling peptide could inhibit the formation of metastatic prostate cancer stem cell colonies in vitro [49]. The result showed that the prostate cancer stem cells DU145 placed in the RADA16-I peptide hydrogel stopped both the division of cancer cells in vitro and subsequent colony formation for up to 28 days.…”

CD44+/CD24- breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold

“…33 Research by Ling et al has suggested that self-assembling peptide can inhibit the formation of metastatic prostate CSC colonies in vitro, while preserving its viability and CSC property. 34 Our results show that the CD44 + /CD24 -cell populationenriched breast cancer cell line adopts various morphologies in different 3D culture scaffolds in response to cues from the extracellular matrix. In this assay, the disorganized malignant phenotype of the cells can partially be reverted to a phenotype much more closely approximating that of nonmalignant breast acini in RADA16 3D cultures.…”

Nanomaterials in controlled drug release

“…Because peptides are synthesized from amino acids, the degradation of the peptidebased scaffolds would lead to no immune response and side effects (Kopecek and Yang 2009;Zhao et al 2010). Moreover, these reported self-assembly peptide nanofiber scaffolds are with high water content, mimicking the natural extracellular matrix, and have been shown to be useful in 3D cell culture, tissue repair, and regeneration (Collier et al 2010;EllisBehnke et al 2006a, b;Guo et al 2007;Kopecek and Yang 2009;Ling et al 2011;Zhao et al 2010). One interesting application is to engineer the peptide molecules with side chains of pharmaceutical effects (Zhao et al 2010), and the hydrogel during biological degradation will guide the drug release reactions.…”