Fluid Flow Dependency in Immunoselective Cell Capture via Liquid Biopsy.

Liquid biopsy targets rare cells that overexpress disease-specific membrane markers and capture these cells via immunoaffinity. The diagnosis efficiency of liquid biopsy can be impaired by the presence of healthy adherent cells also expressing the same biomarkers. Here, we investigated the effect of settling times and rinsing flow rates on the efficiency of EpCAM-based immunocapture using both simulation and experiments with three different cell types. Cell-surface adhesion forces and shear rates were calculated to define the range of rinsing flow rates to test experimentally. Healthy adherent cells did not adhere to blocked immunofunctionalized surfaces within the timeframe of the experiment; however, healthy EpCAM positive cells did bind to the surface to some extent. The greatest difference in capture efficiency was obtained using a high rinsing flow rate of 25 mL/min following 40 min static incubation, indicating that optimizing rinsing flow rates could be a viable option to capture, more specifically, cancer cells overexpressing EpCAM.

In order for the light to shine so brightly, the darkness must be present-why do cancers fluoresce with 5-aminolaevulinic acid?

Photodynamic diagnosis and therapy have emerged as a promising tool in oncology. Using the visible fluorescence from photosensitisers excited by light, clinicians can both identify and treat tumour cells in situ. Protoporphyrin IX, produced in the penultimate step of the haem synthesis pathway, is a naturally occurring photosensitiser that visibly fluoresces when exposed to light. This fluorescence is enhanced considerably by the exogenous administration of the substrate 5-aminolaevulinic acid (5-ALA). Significantly, 5-ALA-induced protoporphyrin IX accumulates preferentially in cancer cells, and this enhanced fluorescence has been harnessed for the detection and photodynamic treatment of brain, skin and bladder tumours. However, surprisingly little is known about the mechanistic basis for this phenomenon. This review focuses on alterations in the haem pathway in cancer and considers the unique features of the cancer environment, such as altered glucose metabolism, oncogenic mutations and hypoxia, and their potential effects on the protoporphyrin IX phenomenon. A better understanding of why cancer cells fluoresce with 5-ALA would improve its use in cancer diagnostics and therapies.

Hydrophobic Coatings with Charge Permeability via Plasma Deposition of Long-Chain Perfluorocarbons.

Hydrophobization of nanotextured catalyst materials is a promising route to enhance the yield of N2 and CO2 conversion into green fuels. However, these applications require a hydrophobic coating to not only promote air trapping but also allow charge transfer at the electrode-electrolyte interface. In this work, nano thin films with thicknesses as low as 7 nm were deposited from the plasma phase of perfluorohexene, perfluorodecene, and perfluorooctane (PFO) precursors using a mild vacuum and gentle powers. Atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) characterization reveal that the resulting films are conformal and hydrophobic thanks to a good retention of CF2 and CF3 moieties. The PFO films exhibited the highest water contact angle and achieved superhydrophobic states when deposited on top of re-entrant nano features, an indication of successful air trapping. Electrochemical studies further demonstrated that the plasma-deposited PFO films allow charge transfer but could only sustain repeated cyclic voltammetry cycles without losing their hydrophobicity when deposited under optimal conditions. This result indicates that plasma deposition could become a viable route for the hydrophobization of electrocatalysts required to enhance the yield of poorly soluble gas reduction reactions.

Nanoparticles Surface Chemistry Influence on Protein Corona Composition and Inflammatory Responses.

Nanoparticles are widely used for biomedical applications such as vaccine, drug delivery, diagnostics, and therapeutics. This study aims to reveal the influence of nanoparticle surface functionalization on protein corona formation from blood serum and plasma and the subsequent effects on the innate immune cellular responses. To achieve this goal, the surface chemistry of silica nanoparticles of 20 nm diameter was tailored via plasma polymerization with amine, carboxylic acid, oxazolines, and alkane functionalities. The results of this study show significant surface chemistry-induced differences in protein corona composition, which reflect in the subsequent inflammatory consequences. Nanoparticles rich with carboxylic acid surface functionalities increased the production of pro-inflammatory cytokines in response to higher level of complement proteins and decreased the number of lipoproteins found in their protein coronas. On another hand, amine rich coatings led to increased expressions of anti-inflammatory markers such as arginase. The findings demonstrate the potential to direct physiological responses to nanomaterials via tailoring their surface chemical composition.

Plasma Polymer Coatings To Direct the Differentiation of Mouse Kidney-Derived Stem Cells into Podocyte and Proximal Tubule-like Cells.

Kidney disease is now recognized as a global health problem and is associated with increased morbidity and mortality, along with high economic costs. To develop new treatments for ameliorating kidney injury and preventing disease progression, there is a need for appropriate renal culture systems for screening novel drugs and investigating the cellular mechanisms underlying renal pathogenesis. There is a need for in vitro culture systems that promote the growth and differentiation of specialized renal cell types. In this work, we have used plasma polymerization technology to generate gradients of chemical functional groups to explore whether specific concentrations of these functional groups can direct the differentiation of mouse kidney-derived stem cells into specialized renal cell types. We found that amine-rich (-NH2) allylamine-based plasma-polymerized coatings could promote differentiation into podocyte-like cells, whereas methyl-rich (CH3) 1,7-octadiene-based coatings promoted differentiation into proximal tubule-like cells (PTC). Importantly, the PT-like cells generated on the substrates expressed the marker megalin and were able to endocytose albumin, indicating that the cells were functional.

Biomaterial Surface Hydrophobicity-Mediated Serum Protein Adsorption and Immune Responses.

The nature of the protein corona forming on biomaterial surfaces can affect the performance of implanted devices. This study investigated the role of surface chemistry and wettability on human serum-derived protein corona formation on biomaterial surfaces and the subsequent effects on the cellular innate immune response. Plasma polymerization, a substrate-independent technique, was employed to create nanothin coatings with four specific chemical functionalities and a spectrum of surface charges and wettability. The amount and type of protein adsorbed was strongly influenced by surface chemistry and wettability but did not show any dependence on surface charge. An enhanced adsorption of the dysopsonin albumin was observed on hydrophilic carboxyl surfaces while high opsonin IgG2 adsorption was seen on hydrophobic hydrocarbon surfaces. This in turn led to a distinct immune response from macrophages; hydrophilic surfaces drove greater expression of anti-inflammatory cytokines by macrophages, whilst surface hydrophobicity caused increased production of proinflammatory signaling molecules. These findings map out a unique relationship between surface chemistry, hydrophobicity, protein corona formation, and subsequent cellular innate immune responses; the potential outcomes of these studies may be employed to tailor biomaterial surface modifications, to modulate serum protein adsorption and to achieve the desirable innate immune response to implanted biomaterials and devices.

Self-sterilizing antibacterial silver-loaded microneedles.

Microneedle patches have become an exciting means for transdermal delivery of various therapeutics. Herein, we report on self-sterilizing dissolving nanosilver-loaded microneedle patches created from carboxymethylcellulose capable of suppressing microbial pathogen growth at the insertion site.