Focused ultrasound-mediated brain genome editing.

Gene editing in the brain has been challenging because of the restricted transport imposed by the blood-brain barrier (BBB). Current approaches mainly rely on local injection to bypass the BBB. However, such administration is highly invasive and not amenable to treating certain delicate regions of the brain.

Focused ultrasound-mediated brain genome editing.

Gene editing in the mammalian brain has been challenging because of the restricted transport imposed by the blood-brain barrier (BBB). Current approaches rely on local injection to bypass the BBB. However, such administration is highly invasive and not amenable to treating certain delicate regions of the brain.

Phenylboronic Acid-Functionalized Polyplexes Tailored to Oral CRISPR Delivery.

Effective delivery of the CRISPR-Cas9 components is crucial to realizing the therapeutic potential. Although many delivery approaches have been developed for this application, oral delivery has not been explored due to the degradative nature of the gastrointestinal tract. For this issue, we developed a series of novel phenylboronic acid (PBA)-functionalized chitosan-polyethylenimine (CS-PEI) polymers for oral CRISPR delivery.

Targeting Proinflammatory Molecules Using Multifunctional MnO Nanoparticles to Inhibit Breast Cancer Recurrence and Metastasis.

Photothermal therapy (PTT) is an effective treatment modality that is highly selective for tumor suppression and is a hopeful alternative to traditional cancer therapy. However, PTT-induced inflammatory responses may result in undesirable side effects including increased risks of tumor recurrence and metastasis. Here we developed multifunctional MnO nanoparticles as scavengers of proinflammatory molecules to alleviate the PTT-induced inflammatory response.

Nanoparticulate cell-free DNA scavenger for treating inflammatory bone loss in periodontitis.

Periodontitis is a common type of inflammatory bone loss and a risk factor for systemic diseases. The pathogenesis of periodontitis involves inflammatory dysregulation, which represents a target for new therapeutic strategies to treat periodontitis. After establishing the correlation of cell-free DNA (cfDNA) level with periodontitis in patient samples, we test the hypothesis that the cfDNA-scavenging approach will benefit periodontitis treatment.

A Cationic Metal-Organic Framework to Scavenge Cell-Free DNA for Severe Sepsis Management.

Circulating cell-free DNA (cfDNA) released by damaged cells causes inflammation and has been associated with the progression of sepsis. One proposed strategy to treat sepsis is to scavenge this inflammatory circulating cfDNA. Here, we develop a cfDNA-scavenging nanoparticle (NP) that consists of cationic polyethylenimine (PEI) of different molecular weight grafted to zeolitic imidazolate framework-8 (PEI--ZIF) in a simple one-pot process.

CRISPR/Cas9-mediated mutagenesis to validate the synergy between PARP1 inhibition and chemotherapy in -mutated breast cancer cells.

For patients carrying mutations, at least one-third develop triple negative breast cancer (TNBC). Not only is TNBC difficult to treat due to the lack of molecular target receptors, but mutations (BRCA1m) also result in chemotherapeutic resistance, making disease recurrence more likely. Although BRCA1m are highly heterogeneous and therefore difficult to target, gene's synthetic lethal pair, , is conserved in BRCA1m cancer cells.

Engineered Mesenchymal Stem Cell/Nanomedicine Spheroid as an Active Drug Delivery Platform for Combinational Glioblastoma Therapy.

Mesenchymal stem cell (MSC) has been increasingly applied to cancer therapy because of its tumor-tropic capability. However, short retention at target tissue and limited payload option hinder the progress of MSC-based cancer therapy. Herein, we proposed a hybrid spheroid/nanomedicine system, comprising MSC spheroid entrapping drug-loaded nanocomposite, to address these limitations.

Near-Infrared Fluorescent Nanoprobes for in Vivo Optical Imaging.

Near-infrared (NIR) fluorescent probes offer advantages of high photon penetration, reduced light scattering and minimal autofluorescence from living tissues, rendering them valuable for noninvasive mapping of molecular events, assessment of therapeutic efficacy, and monitoring of disease progression in animal models. This review provides an overview of the recent development of the design and optical property of the different classes of NIR fluorescent nanoprobes associated with in vivo imaging applications.

A dual-functional fibrous scaffold enhances P450 activity of cultured primary rat hepatocytes.

We have designed a novel dual-functional electrospun fibrous scaffold comprising two fiber mesh layers that were modified differently to induce two separate biological responses from hepatocytes. The first fiber layer was galactosylated on the surface to mediate hepatocyte attachment, while the second layer was loaded with 3-methylcholanthrene (3-Mc) to enhance cytochrome P450 activity of hepatocytes. Primary rat hepatocytes cultured on the galactosylated fibrous scaffolds loaded with different concentrations of 3-Mc were compared for their cell attachment efficiency, albumin secretion activity and cytochrome P450-dependent 7-ethoxycoumarin O-deethylase activity.

The zwitterion effect in proton exchange membranes as synthesised by polymerisation of bicontinuous microemulsions.

The bicontinuous microemulsions consisting of a polymerisable zwitterionic surfactant 3-((11-acryloyloxyundecyl)imidazolyl) propyl sulfonate (AIPS) and other monomers can be cross-polymerised to form good proton conductive membranes.

Engineering microenvironment for expansion of sensitive anchorage-dependent mammalian cells.

Tissue engineering involves ex vivo seeding of anchorage-dependent mammalian cells onto scaffolds, or transplanting cells in vivo. The cell expansion currently requires repeated cell detachment from solid substrata by enzymatic, chemical or mechanical means. The report here presents a high yield three-dimensional culture and harvest system circumventing the conventional detachment requirements.

Encapsulating live cells with water-soluble chitosan in physiological conditions.

A new class of microcapsules was prepared under physiological conditions by polyelectrolyte complexation between two oppositely-charged, water-soluble polymers. The microcapsules consisted of an inner core of half N-acetylated chitosan and an outer shell of methacrylic acid (MAA) (20.4%)-hydroxyethyl methacrylate (HEMA) (27.

Quantitative measurement of collagen methylation by capillary electrophoresis.

Collagen methylation has been exploited in various applications involving living cells. We have observed correlation between the collagen methylation with the rate of cell proliferation in three-dimensional (3-D) microenvironment. To quantify the degree of collagen methylation, we have developed a capillary zone electrophoresis method.

Photo-crosslinkable microcapsules formed by polyelectrolyte copolymer and modified collagen for rat hepatocyte encapsulation.

New anionic polyelectrolyte tetra-copolymers with photo-crosslinkable 4-(4-methoxycinnamoyl)phenyl methacrylate monomer in addition to a HEMA-MMA-MAA ter-copolymer system were synthesized. The tetra-copolymers were used to form photo-crosslinkable microcapsules with modified collagen by complex coacervation for rat hepatocytes encapsulation. The hepatocytes were encapsulated within a two-layered membrane comprising of modified collagen as the inner core and an outer photo-crosslinkable copolymer shell.

Use of ultrathin shell microcapsules of hepatocytes in bioartificial liver-assist device.

We previously encapsulated hepatocytes in ultrathin shell microcapsules and showed them to have enhanced differentiated functions over cells cultured in monolayer. Here we have used these microencapsulated hepatocytes in a bioartificial liver-assisted device (BLAD) with a rat hepatectomy model. Primary rat hepatocytes were encapsulated in 150- to 200-microm microcapsules, using an electrostatic droplet generator.

Nanoparticles of polystyrene latexes by semicontinuous microemulsion polymerization using mixed surfactants.

Nanosized polystyrene (PS) latexes stabilized by the mixture of cationic/cationic, anionic/anionic, or anionic/cationic surfactants of various types with high weight ratios of PS to surfactant (ca. 10:1) have been successfully synthesized by a semicontinuous microemulsion polymerization process. For cationic or anionic systems, spherical latex particles with a weight-averaged diameter (Dw) ranging from about 22 to 53 nm were nearly linearly dependent on the weight ratio of the mixed surfactants with similar charges.

Microcapsules with improved mechanical stability for hepatocyte culture.

Packed-bed or fluidized-bed bioreactor filled with microencapsulated hepatocytes has been proposed as one of the promising designs for bioartificial liver assist device (BLAD) because of potential advantages of high mass transport rate and optimal microenvironment for hepatocyte culture. Recently, we have developed a microcapsule system for the encapsulation of hepatocytes. The microcapsules consist of an inner core of modified collagen and an outer shell of terpolymer of methyl methacrylate, methacrylate and hydroxyethyl methacrylate.