Malignant tumors are often associated with an elevated fluid pressure due to the abnormal growth of vascular vessels, and thus an increased interstitial flow out of the tumor. Recent in vitro work revealed that interstitial flows critically regulated tumor cell migration within a three dimensional biomatrix, and breast cancer cell migration behavior depended sensitively on the cell seeding density, chemokine availability and flow rates. In this paper, we focus on roles of interstitial flows in modulating heterogeneity of cancer cell motility phenotype within a three dimensional biomatrix. Using a newly developed microfluidic model, we show that breast cancer cells (MDA-MB-231) embedded in a 3D type I collagen matrix exhibit both an amoeboid and a mesenchymal motility, and interstitial flows promote the cell population towards the amoeboid motility phenotype. Furthermore, the addition of exogenous adhesion molecules (fibronectin) within the extracellular matrix (type I collagen) partially rescues the mesenchymal phenotype in the presence of the flow. Quantitative analysis of cell tracks and cell shape shows distinct differential migration characteristics of amoeboid and mesenchymal cells. Notably, the fastest moving cells belong to the subpopulation of amoeboid cells. Together, these findings highlight the important roles of biophysical forces in modulating tumor cell migration heterogeneity and plasticity, as well as the suitability of microfluidic models in interrogating tumor cell dynamics at single-cell and subpopulation level.

A novel approach for the preparation of dual-functional carbon dots, i.e., nitrogen- and chloride-doped carbon dots, abbreviated as N/Cl-CDs, is developed with the assistance of a choline chloride-glycerine deep eutectic solvent (DES). The carbon source is provided by urea and the DES serves as a solvent for controlling the preparation of CDs in the absence of water. The dual-element doped carbon dots are oxygen-rich with hydroxyl and amine groups. They exhibit an average particle size of ca. 3.88 nm and give rise to strong and pH-sensitive fluorescent emission at λ/λ = 340/430 nm with a quantum yield of 16.15 ± 1.36%. It is particularly interesting to see that the fluorescence of N/Cl-CDs remains stable in a high-salinity matrix, providing vast potentials for treating real biological sample matrixes with high salinity. The N/Cl-CDs provide an optical probe for intracellular pH sensing and multicolor imaging in HeLa cells. In addition, the N/Cl-CDs show obvious fluorescence response to cytochrome c (cyt- c) with a detection limit of 3.6 mg L (ca. 0.29 μmol L) within in a range of 10-500 mg L, providing potentials for fluorescence detection of cyt- c as well as facilitating intracellular cyt- c imaging.

Here we report a novel mechanism for triggering drug release in the polydopamine (PDA)-coated magnetic CuCo2S4 core–shell nanostructure by glutathione (GSH) triggered degradation of PDA for release.