Long-Term Stable and Multifeature Microfluidic Impedance Flow Cytometry Based on a Constricted Channel for Single-Cell Mechanical Phenotyping.

The microfluidic impedance flow cytometer (m-IFC) using constricted microchannels is an appealing choice for the high-throughput measurement of single-cell mechanical properties. However, channels smaller than the cells are susceptible to irreversible blockage, extremely affecting the stability of the system and the throughput. Meanwhile, the common practice of extracting a single quantitative index, i.

Biomimetic nanodecoys deliver cholesterol-modified heteroduplex oligonucleotide to target dopaminergic neurons for the treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of α-synuclein (α-syn) aggregates called Lewy bodies leading to the gradual loss of dopaminergic (DA) neurons in the substantia nigra. Although α-syn expression can be attenuated by antisense oligonucleotides (ASOs) and heteroduplex oligonucleotide (HDO) by intracerebroventricular (ICV) injection, the challenge to peripheral targeted delivery of oligonucleotide safely and effectively into DA neurons remains unresolved. Here, we designed a new DNA/DNA double-stranded (complementary DNA, coDNA) molecule with cholesterol conjugation (Chol-HDO (coDNA)) based on an α-syn-ASO sequence and evaluated its silence efficiency.

Microfluidic characterization of single-cell biophysical properties and the applications in cancer diagnosis.

Single-cell biophysical properties play a crucial role in regulating cellular physiological states and functions, demonstrating significant potential in the fields of life sciences and clinical diagnostics. Therefore, over the last few decades, researchers have developed various detection tools to explore the relationship between the biophysical changes of biological cells and human diseases. With the rapid advancement of modern microfabrication technology, microfluidic devices have quickly emerged as a promising platform for single-cell analysis offering advantages including high-throughput, exceptional precision, and ease of manipulation.

A microfluidic array enabling generation of identical biochemical stimulating signals to trapped biological cells for single-cell dynamics.

Microfluidic-based analyses of single-cell dynamics in response to dynamic biochemical signals are emerging as pivotal approaches for investigating the effects of extracellular microenvironmental biochemical factors on cellular structure, function, and behavior. However, current devices often fail to consistently apply identical dynamic biochemical signals to trapped cells. In this study, we introduce a novel radially distributed single-cell trapping microfluidic array, designed to quantitatively and consistently apply identical biochemical stimulating signals to each trapped cell.

A mathematical model for intracellular NO and ROS dynamics in vascular endothelial cells activated by exercise-induced wall shear stress.

Vascular endothelial cells (ECs) residing in the innermost layer of blood vessels are exposed to dynamic wall shear stress (WSS) induced by blood flow. The intracellular nitric oxide (NO) and reactive oxygen species (ROS) in ECs modulated by the dynamic WSS play important roles in endothelial functions. Mathematical modeling is a popular methodology for biophysical studies.

Nonviral delivery systems for antisense oligonucleotide therapeutics.

Antisense oligonucleotides (ASOs) are an important tool for the treatment of many genetic disorders. However, similar to other gene drugs, vectors are often required to protect them from degradation and clearance, and to accomplish their transport in vivo. Compared with viral vectors, artificial nonviral nanoparticles have a variety of design, synthesis, and formulation possibilities that can be selected to accomplish protection and delivery for specific applications, and they have served critical therapeutic purposes in animal model research and clinical applications, allowing safe and efficient gene delivery processes into the target cells.

Apoptotic bodies for advanced drug delivery and therapy.

Extracellular vesicles (EVs) have emerged as promising candidates for multiple biomedical applications. Major types of EVs include exosomes, microvesicles, and apoptotic bodies (ABs). ABs are conferred most properties from parent cells in the final stages of apoptosis.

Fabricating a multi-component microfluidic system for exercise-induced endothelial cell mechanobiology guided by hemodynamic similarity.

Generating precise in vivo arterial endothelial hemodynamic microenvironments using microfluidics is essential for exploring endothelial mechanobiology. However, a hemodynamic principle guiding the fabrication of microfluidic systems is still lacking. We propose a hemodynamic similarity principle for quickly obtaining the input impedance of the microfluidic system in vitro derived from that of the arterial system in vivo to precisely generate the desired endothelial hemodynamic microenvironments.

Hybrid Cell Membrane-Functionalized Biomimetic Nanoparticles for Targeted Therapy of Osteosarcoma.

Purpose: In order to prepare a biomimetic nano-carrier which has inflammatory chemotaxis, homologous targeting and reduce immune clearance, for targeted chemotherapy of osteosarcoma, we fabricated the paclitaxel-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles coated with 143B-RAW hybrid membrane (PTX-PLGA@[143B-RAW] NPs) and evaluate its anti-cancer efficacy in vitro and vivo.

Methods: PTX-PLGA@[143B-RAW] NPs were prepared by the ultrasonic method and were characterized by size, zeta potential, polymer dispersion index (PDI), Coomassie bright blue staining, transmission electron microscopy (TEM) and high performance liquid chromatography (HPLC). Cellular uptake, cell viability assay, flow cytometry and chemotactic effect of PTX-PLGA@[143B-RAW] NPs were evaluated in vitro.

Recent progress of macrophage vesicle-based drug delivery systems.

Nanoparticle drug delivery systems (NDDSs) are promising platforms for efficient delivery of drugs. In the past decades, many nanomedicines have received clinical approval and completed translation. With the rapid advance of nanobiotechnology, natural vectors are emerging as novel strategies to carry and delivery nanoparticles and drugs for biomedical applications.

Multifunctional exosome-mimetics for targeted anti-glioblastoma therapy by manipulating protein corona.

Targeted drug delivery to the glioblastoma (GBM) overcoming blood-brain barrier (BBB) has been challenging. Exosomes are promising vehicles for brain tumor drug delivery, but the production and purification hinder its application for nanomedicine. Besides, the formation of protein corona (PC) may affect the behaviour of nanocarriers.

A microfluidic system for precisely reproducing physiological blood pressure and wall shear stress to endothelial cells.

To reproduce hemodynamic stress microenvironments of endothelial cells is of vital significance, by which one could exploit the quantitative impact of hemodynamic stresses on endothelial function and seek innovative approaches to prevent circulatory system diseases. Although microfluidic technology has been regarded as an effective method to create physiological microenvironments, a microfluidic system to precisely reproduce physiological arterial hemodynamic stress microenvironments has not been reported yet. In this paper, a novel microfluidic chip consisting of a cell culture chamber with on-chip afterload components designed by the principle of input impedance to mimic the global hemodynamic behaviors is proposed.

Artificial exosomes for translational nanomedicine.

Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes.

A microfluidic generator of dynamic shear stress and biochemical signals based on autonomously oscillatory flow.

Biological cells in vivo typically reside in a dynamic flowing microenvironment with extensive biomechanical and biochemical cues varying in time and space. These dynamic biomechanical and biochemical signals together act to regulate cellular behaviors and functions. Microfluidic technology is an important experimental platform for mimicking extracellular flowing microenvironment in vitro.

Exosomes and biomimetic nanovesicles-mediated anti-glioblastoma therapy: A head-to-head comparison.

Exosomes (Exos) are promising vehicles for brain drug delivery due to nanosize and the ability to breach the blood-brain barrier (BBB). But the low yield of natural exosomes limits its application for nanomedicine. The generation of bioinspired nanovesicles (BNVs) that mimicking Exos is attractive, but there is a lack of comparative evaluation of Exos and BNVs.

An Optimized Integrin α6-Targeted Magnetic Resonance Probe for Molecular Imaging of Hepatocellular Carcinoma in Mice.

Introduction: Integrin α6 is an attractive diagnostic biomarker for molecular imaging of hepatocellular carcinoma (HCC) as it has an extremely high positive rate (approximately 94%) in clinical early-stage HCC. In this study, based on our previously identified integrin α6-targeted peptide, we developed an optimized integrin α6-targeted magnetic resonance (MR) probe dubbed DOTA(Gd)-ANADYWR for MR imaging of HCC in mice.

Materials And Methods: The longitudinal (R) relaxivity of DOTA(Gd)-ANADYWR was measured on a 3.

Biomimetic Liposome with Surface-Bound Elastase for Enhanced Tumor Penetration and Chemo-Immumotherapy.

Dense extracellular matrix (ECM) in the tumor stroma has been a challenge for drug penetration and cytotoxic T lymphocyte (CTL) infiltration. Neutrophil elastase (NE), in surface-bound form, can destruct ECM rapidly, may be used for remodeling tumor ECM, and overcoming tumor stromal barrier. Focusing on elastosis in triple-negative breast tumor, biomimetic liposomes with chimeric cell membrane proteins (LMP) are developed and for the first time, it is demonstrated that LMP with surface-bound elastase (NE-LMP) can target and degrade ECM effectively in tumor stroma, with minimal toxicity to normal tissues.

From blood to brain: blood cell-based biomimetic drug delivery systems.

Brain drug delivery remains a major difficulty for several challenges including the blood-brain barrier, lesion spot targeting, and stability during circulation. Blood cells including erythrocytes, platelets, and various subpopulations of leukocytes have distinct features such as long-circulation, natural targeting, and chemotaxis. The development of biomimetic drug delivery systems based on blood cells for brain drug delivery is growing fast by using living cells, membrane coating nanotechnology, or cell membrane-derived nanovesicles.

Comparative evaluation of methods for isolating small extracellular vesicles derived from pancreatic cancer cells.

Background: Small extracellular vesicles (sEVs) are nanosized vesicles involved in cell-to-cell communication. sEVs have been widely studied for clinical applications such as early detection of diseases and as therapeutics. Various methods for sEVs isolation are been using, but different methods may result in different qualities of sEVs and impact downstream analysis and applications.

Preservation of small extracellular vesicles for functional analysis and therapeutic applications: a comparative evaluation of storage conditions.

Extracellular vesicles (EVs) are nanovesicles involved in multiple biological functions. Small EVs (sEVs) are emerging as therapeutics and drug delivery systems for their contents, natural carrier properties, and nanoscale size. Despite various clinical application potentials, little is known about the effects of storage conditions on sEVs for functional analysis and therapeutic use.

Emerging strategies for labeling and tracking of extracellular vesicles.

Extracellular vesicles (EVs) are cell-derived lipid bilayer-enclosed nanovesicles. EVs are emerging as keys for identifying molecular mechanisms by mediating intercellular communication. EVs allow the exchange of various components with neighboring and distant cells through the extracellular environment, thereby involving in various biological processes in both physiological and pathological conditions such as wound healing, immune response, and tumorigenesis.