Probing Membrane Viscosity and Interleaflet Friction of Supported Lipid Bilayers by Tracking Electrostatically Adsorbed,Nano‐Sized Vesicles

Particle tracking is used to measure the diffusional motion of nanosized (≈100 nm), lipid vesicles that are electrostatically adsorbed onto a solid supported lipid bilayer. It is found that the motion of membrane‐adhering vesicles is Brownian and depends inversely on the vesicle size, but is insensitive to the vesicle surface charge. The measured diffusivity agrees well with the Evans–Sackmann model for the diffusion of inclusions in supported, fluidic membranes. The agreement implies that the vesicle motion is coupled to that of a nanoscopic lipid cluster in the upper leaflet, which slides over the lower leaflet. The diffusivity of membrane‐adhering vesicles is therefore predominantly governed by the interleaflet friction coefficient, while the diffusivity of single lipids is mainly governed by the membrane viscosity. Combined with fluorescence recovery after photobleaching analysis, the interleaflet friction coefficient and the membrane viscosity are determined by applying the Evans–Sackmann model to the measured diffusivity of membrane adhering vesicles and that of supported membrane lipids. This approach provides an alternative to existing methods for measuring the interleaflet friction coefficient and the membrane viscosity.     

Biomineralized Bacterial Outer Membrane Vesicles Potentiate Safe and Efficient Tumor Microenvironment Reprogramming for Anticancer Therapy

The highly immunosuppressive tumor microenvironment (TME) in solid tumors often dampens the efficacy of immunotherapy. In this study, bacterial outer membrane vesicles (OMVs) are demonstrated as powerful immunostimulants for TME reprogramming. To overcome the obstacles of antibody-dependent clearance and high toxicity induced by OMVs upon intravenous injection (a classic clinically relevant delivery mode), calcium phosphate (CaP) shells are employed to cover the surface of OMVs, which enables potent OMV-based TME reprograming without side effects. Meanwhile, the pH-sensitive CaP shells facilitate the neutralization of acidic TME, leading to highly beneficial M2-to-M1 polarization of macrophages for improved antitumor effect. Moreover, the outer shells can be integrated with functional components like folic acid or photosensitizer agents, which facilitates the use of the OMV-based platform in combination therapies for a synergic therapeutic effect.     

Multifunctional Transmembrane Protein Ligands for Cell‐Specific Targeting of Plasma Membrane‐Derived Vesicles

Liposomes and nanoparticles that bind selectively to cell‐surface receptors can target specific populations of cells. However, chemical conjugation of ligands to these particles is difficult to control, frequently limiting ligand uniformity and complexity. In contrast, the surfaces of living cells are decorated with highly uniform populations of sophisticated transmembrane proteins. Toward harnessing cellular capabilities, here it is demonstrated that plasma membrane vesicles (PMVs) derived from donor cells can display engineered transmembrane protein ligands that precisely target cells on the basis of receptor expression. These multifunctional targeting proteins incorporate (i) a protein ligand, (ii) an intrinsically disordered protein spacer to make the ligand sterically accessible, and (iii) a fluorescent protein domain that enables quantification of the ligand density on the PMV surface. PMVs that display targeting proteins with affinity for the epidermal growth factor receptor (EGFR) bind at increasing concentrations to breast cancer cells that express increasing levels of EGFR. Further, as an example of the generality of this approach, PMVs expressing a single‐domain antibody against green fluorescence protein (eGFP) bind to cells expressing eGFP‐tagged receptors with a selectivity of ≈50:1. The results demonstrate the versatility of PMVs as cell targeting systems, suggesting diverse applications from drug delivery to tissue engineering.     

Adipose‐Derived Biogenic Nanoparticles for Suppression of Inflammation

Extracellular vesicles secreted from adipose‐derived mesenchymal stem cells (ADSCs) have therapeutic effects in inflammatory diseases. However, production of extracellular vesicles (EVs) from ADSCs is costly, inefficient, and time consuming. The anti‐inflammatory properties of adipose tissue‐derived EVs and other biogenic nanoparticles have not been explored. In this study, biogenic nanoparticles are obtained directly from lipoaspirate, an easily accessible and abundant source of biological material. Compared to ADSC‐EVs, lipoaspirate nanoparticles (Lipo‐NPs) take less time to process (hours compared to months) and cost less to produce (clinical‐grade cell culture facilities are not required). The physicochemical characteristics and anti‐inflammatory properties of Lipo‐NPs are evaluated and compared to those of patient‐matched ADSC‐EVs. Moreover, guanabenz loading in Lipo‐NPs is evaluated for enhanced anti‐inflammatory effects. Apolipoprotein E and glycerolipids are enriched in Lipo‐NPs compared to ADSC‐EVs. Additionally, the uptake of Lipo‐NPs in hepatocytes and macrophages is higher. Lipo‐NPs and ADSC‐EVs have comparable protective and anti‐inflammatory effects. Specifically, Lipo‐NPs reduce toll‐like receptor 4‐induced secretion of inflammatory cytokines in macrophages. Guanabenz‐loaded Lipo‐NPs further suppress inflammatory pathways, suggesting that this combination therapy can have promising applications for inflammatory diseases.     

Isolation and Profiling of Circulating Tumor‐Associated Exosomes Using Extracellular Vesicular Lipid–Protein Binding Affinity Based Microfluidic Device

Extracellular vesicles (EVs) are emerging as a potential diagnostic test for cancer. Owing to the recent advances in microfluidics, on‐chip EV isolation is showing promise with respect to improved recovery rates, smaller necessary sample volumes, and shorter processing times than ultracentrifugation. Immunoaffinity‐based microfluidic EV isolation using anti‐CD63 is widely used; however, anti‐CD63 is not specific to cancer‐EVs, and some cancers secrete EVs with low expression of CD63. Alternatively, phosphatidylserine (PS), usually expressed in the inner leaflet of the lipid bilayer of the cells, is shown to be expressed on the outer surface of cancer‐associated EVs. A new exosome isolation microfluidic device (^newExoChip), conjugated with a PS‐specific protein, to isolate cancer‐associated exosomes from plasma, is presented. The device achieves 90% capture efficiency for cancer cell exosomes compared to 38% for healthy exosomes and isolates 35% more A549‐derived exosomes than an anti‐CD63‐conjugated device. Immobilized exosomes are then easily released using Ca²⁺ chelation. The recovered exosomes from clinical samples are characterized by electron microscopy and western‐blot analysis, revealing exosomal shapes and exosomal protein expressions. The ^newExoChip facilitates the isolation of a specific subset of exosomes, allowing the exploration of the undiscovered roles of exosomes in cancer progression and metastasis.     

Superior Cryogenic Tensile Strength and Ductility of In Situ Al–Cu Matrix Composite Reinforced with 0.3 wt% Nano‐Sized TiCp

In the present work, the tensile properties at 77 K of the 0.3 wt% nano‐sized TiC_p/Al–Cu composite is investigated to explore its potential application at cryogenic temperature. The TiC_p/Al–Cu composite exhibits superior ultimate tensile strength (620 MPa), yield strength (531 MPa), and fracture strain (7.2%) at 77 K. The addition of TiC_p leads to the refinement of θ′ precipitates and enhanced dislocation strengthening effect, contributing to the improved tensile strength.

     

In vivo correlation between semi‐quantitative hemodynamic parameters and Ktrans derived from DCE‐MRI of brain tumors

Dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) has become more and more widely applied in cancer diagnosis and treatment follow‐up. Without complicated calculation, a semiquantitative parameter – modified initial area under the curve (mIAUC_c) – was proposed for better correlation with volume transfer constant (K^trans) by computer simulation. In this study, we aim to further investigate the correlation between mIAUC_c and K^trans in clinical. A total of 10 patients with brain tumors participated in this study and images were acquired by using a 3‐Tesla clinical MR scanner. The results showed that mIAUC_c was highly correlated with K^trans with the correlation coefficient of 0.913. Although the ideals of K^trans and mIAUC_c are different, mIAUC_c does the trick for brain tumors evaluations in DCE‐MRI. It reveals that mIAUC_c could be an alternative for physiological condition evaluation in DCE‐MRI. © 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 132–136, 2012