Acute cerebral infarction (ACI) is a lethal disease whose early diagnosis is critical for treatment. microRNA (miR)-19a targets CC chemokine ligand 20 (CCL20) in myocardial infarction. We investigated the expression patterns of serum miR-19a and CCL20 of ACI patients and assessed their clinical values. Serum samples of 50 healthy subjects and110 ACI patients were collected. Serum levels of miR-19a, CCL20 mRNA, and biochemical indexes were assessed. miR-19a downstream target gene and the binding relationship between miR-19a and CCL20 were predicted and verified. miR-19a and CCL20 mRNA were subjected to correlation and diagnostic efficiency analysis. miR-19a was poorly expressed in the serum of ACI patients, especially in patients with unstable plaque and large infarction. tumor necrosis factor-α, low-density lipoprotein, and platelet/lymphocyte ratio negatively correlated with serum miR-19a level and positively correlated with CCL20. Dual-luciferase assay revealed that miR-19a could negatively regulate CCL20 expression. CCL20 was highly expressed in the serum of ACI patients. The area under receiver-operating characteristic curve of miR-19a combined with CCL20 was 0.9741 (98.00% specificity, 90.91% sensitivity), higher than their single diagnosis. Collectively, miR-19a had high diagnostic value for ACI and could target to restrain CCL20. The combination of miR-19a and CCL20 improved diagnostic value for ACI.

The epidermal growth factor receptor (EGFR) has become an important target protein in anticancer drug development. Meanwhile, peptide-Au cluster has been proposed as potential targeted nano-drug assembled by targeting peptide. Here, we designed and synthesized a novel peptide-Au cluster as Au10Peptide5 to target to EGFR. We found Au10Peptide5 could target to the natural binding sites of all EGFRs at membrane in both active and inactive states by molecular simulations. Its targeted ability was further verified by the co-localization and blocking experiments. We also study the configuration modifications of both active and inactive EGFRs after binding by Au10Peptide5. For active EGFR, the absorbed Au10Peptide5 might replace the natural ligand in EGFR endocytosis process. Then, the peptide-Au cluster in endochylema could inhibit the cancer relating enzyme activity including thioredoxin reductase1 (TrxR1) and induce the oxidative stress mediated apoptosis in tumor cells. For inactive EGFR, it was retained in inactive state by Au10Peptide5 binding to inhibit dimerization of EGFR for anticancer. Both pathways might be applied in anticancer drug development based on the theoretical and experimental study here.

The effectiveness of most in situ remedial technologies, including nanoremediation, lies on successful delivery of reagents to a subsurface target treatment zone. Targeted delivery of engineered nanoparticles (NPs) to treat petroleum hydrocarbons present in the unsaturated zone requires an understanding of their transport behaviour in these systems. A series of column experiments explored the effect of initial water saturation, flowrate, input dosage, and porous medium texture on the transport of iron oxide or cobalt ferrite NPs coated with an amphiphilic co-polymer, as well as their targeted attachment to a crude oil zone. As the initial water content increased with a concomitant reduction in air saturation, the degree of tailing present in the NP breakthrough curves (BTCs) reduced, and the mass of NPs recovered increased. Air saturation is positively correlated with the magnitude of air-water interfaces, which provide additional NP retention sites. At a lower injection flow rate, NP retention increased due to a longer residence time and comparatively high air saturation. NP transport behaviour was not sensitive to NP injection dose over the range tested. Increased retention and retardation of the NP BTC was observed in sediments with a higher clay and silt content. NPs coated with a lower concentration of a Pluronic block co-polymer to promote binding were preferentially retained within the crude oil zone. To simulate the asymmetrical NP breakthrough curves observed from the unsaturated systems required the use of a model that accounted for both mobile and immobile flow regions as well as NP attachment and detachment with nonlinear Langmuirian blocking. This model allowed examination of attachment and detachment rate coefficients which captured NP interaction with the porous medium and/or crude oil. It was found that the initial water saturation and flow rate did not have an appreciable impact on the NP attachment rate coefficient, while it increased by ~10× with increasing clay and silt content, and by ~100× in the presence of crude oil, indicating preferential NP attachment within the crude oil zone. As a result of the lower NP polymer concentration coating used to promote increased attachment to crude oil, higher retention was observed near the column inlet and was captured quantitatively by adding a depth-dependent straining term to the model. This retention behaviour represents a combination of irreversible attachment at the air-water interfaces and straining near the column inlet enhanced by the formation of NP aggregates. The detachment rate coefficient decreased with a lower initial water saturation and flowrate, but increased with higher clay and silt content. The findings from this study contribute to our understanding of the transport and binding behaviour of Pluronic-coated NPs in unsaturated conditions and, in particular, the role of initial water content, flowrate and porous medium texture. Demonstrated delivery of NPs to a target zone is an important step towards expanding the utility of NPs as treatment reagents.

The ongoing problem with the thrombogenicity and poor tissue integration of synthetic vascular grafts demands the design of new surfaces that simultaneously suppress thrombosis and promote endothelialization. Lubricant-infused surfaces have shown outstanding results in preventing clot formation; however, their innate ability to completely block the surface, averts targeted binding of desired biomolecules. We report a new class of expanded polytetrafluoroethylene (ePTFE) vascular grafts that prevent blood coagulation and concurrently promote endothelial cell adhesion. This is made possible by direct silanization of anti-CD34 antibody with the coupling agent and subsequent conjugation of the silanized antibody to the ePTFE surface. In contrast to the conventional methods, we eliminated the need to chemically modify the ePTFE substrate for attaching the capturing ligand, and as a result preserved the innate surface properties of the ePTFE substrate. This is crucial for infiltrating the fluorine-based ePTFE substrate with a biocompatible perfluorocarbon-based lubricant and ultimately creating a functional and stable lubricant-infused layer. Compared to commercially available ePTFE vascular grafts and the ones coated using conventional methods, our developed ePTFE grafts significantly attenuate thrombin generation and blood clot formation and specifically capture endothelial cells from human whole blood while preventing nonspecific adhesion of undesirable proteins and cells. The developed technology can be applied to other biomarkers and biomaterials and can be tailored toward different biomedical applications where biofunctionality and targeted binding are of importance.

New surface coatings that enhance hemocompatibility and biofunctionality of synthetic vascular grafts such as expanded poly(tetrafluoroethylene) (ePTFE) and poly(ethylene terephthalate) (PET) are urgently needed. Lubricant-infused surfaces prevent nontargeted adhesion and enhance the biocompatibility of blood-contacting surfaces. However, limited success has been made in incorporating biofunctionality onto these surfaces and generating biofunctional lubricant-infused coatings that both prevent nonspecific adhesion and enhance targeted binding of biomolecules remains a challenge. Here, a new generation of fluorosilanized lubricant-infused PET surfaces with built-in biofunctional nanoprobes is reported. These surfaces are synthesized by starting with a self-assembled monolayer of fluorosilane that is partially etched using plasma modification technique, thereby creating a hydroxyl-terminated fluorosilanized PET surface. Simultaneously, silanized nanoprobes are produced by amino-silanizing anti-CD34 antibody in solution and directly coupling the anti-CD34-aminosilane nanoprobes onto the hydroxyl terminated, fluorosilanized PET surface. The PET surfaces are then lubricated, creating fluorosilanized biofunctional lubricant-infused PET substrates. Compared with unmodified PET surfaces, the designed biofunctional lubricant-infused PET surfaces significantly attenuate thrombin generation and blood clot formation and promote targeted binding of endothelial cells from human whole blood.

Lubricant-infused omniphobic surfaces have exhibited outstanding effectiveness in inhibiting nonspecific adhesion and attenuating superimposed clot formation compared with other coated surfaces. However, such surfaces blindly thwart adhesion, which is troublesome for applications that rely on targeted adhesion. Here we introduce a new class of lubricant-infused surfaces that offer tunable bioactivity together with omniphobic properties by integrating biofunctional domains into the lubricant-infused layer. These novel surfaces promote targeted binding of desired species while simultaneously preventing nonspecific adhesion. To develop these surfaces, mixed self-assembled monolayers (SAMs) of aminosilanes and fluorosilanes were generated. Aminosilanes were utilized as coupling molecules for immobilizing capture ligands, and nonspecific adhesion of cells and proteins was prevented by infiltrating the fluorosilane molecules with a thin layer of a biocompatible fluorocarbon-based lubricant, thus generating biofunctional lubricant-infused surfaces. This method yields surfaces that (a) exhibit highly tunable binding of anti-CD34 and anti-CD144 antibodies and adhesion of endothelial cells, while repelling nonspecific adhesion of undesirable proteins and cells not only in buffer but also in human plasma or human whole blood, and (b) attenuate blood clot formation. Therefore, this straightforward and simple method creates biofunctional, nonsticky surfaces that can be used to optimize the performance of devices such as biomedical implants, extracorporeal circuits, and biosensors.

Integrin αVβ3-targeting peptides with an exposed arginine-glycine-aspartate (RGD) sequence play a crucial role in targeted anticancer drug delivery. The effects of RGD-containing peptide structure and quantity on mechanism of targeted binding of RGD-containing peptide to integrin αVβ3 were studied intensively at the molecular level via molecular dynamic simulations. Targeted recognization was mainly driven by the electrostatic interactions between the residues in RGD and the metal ions in integrin αVβ3, and cyclic arginine-glycine-aspartate-phenylalanine-valine (RGDFV) peptide appeared to be a better vector than the linear RGD-containing peptides. In addition, the optimal molar concentration ratio of RGD peptides to integrin αVβ3 appeared to be 2:1. These results will help improve the current understanding on the mechanism of interactions between RGD and integrin αVβ3, and promote the application prospects of RGD-based vectors in tumor imaging, diagnosis, and cancer therapy.