NIR-Induced Photoswitching Hybrid DNA Nanoconstruct-Based Drug Delivery System for Spatiotemporal Control of Stem Cell Fate.

Precise spatiotemporal control of drug delivery is extremely valuable for regulating stem cell fate, particularly in stem cell differentiation. A novel near-infrared (NIR)-mediated spatiotemporal delivery system is reported combining photo-switchable arylazopyrazole (AAP)-containing DNA strands and upconversion nanoparticles (UCNPs). This nano-drug delivery system (NDDS) enables precise modulation of DNA duplex structures in response to NIR stimuli, overcoming the limitations of traditional UV-responsive systems.

OrthologAL: A Shiny application for quality-aware humanization of non-human pre-clinical high-dimensional gene expression data.

Single-cell and spatial transcriptomics provide unprecedented insight into the inner workings of disease. Pharmacotranscriptomic approaches are powerful tools that leverage gene expression data for drug repurposing and treatment discovery in many diseases. Multiple databases attempt to connect human cellular transcriptional responses to small molecules for use in transcriptome-based drug discovery efforts.

In Situ Detection of Neuroinflammation using Multi-cellular 3D Neurovascular Unit-on-a-Chip.

The human neurovascular system is a complex network of blood vessels and brain cells that is essential to the proper functioning of the brain. In recent years, researchers have become increasingly interested in the role of this system in developing drugs to treat neuroinflammation. This process is believed to contribute to the development of several neurodegenerative diseases, including Alzheimer's and Parkinson's diseases.

Real-Time, Non-Invasive Monitoring of Neuronal Differentiation Using Intein-Enabled Fluorescence Signal Translocation in Genetically Encoded Stem Cell-Based Biosensors.

Real-time and non-invasive monitoring of neuronal differentiation will help increase our understanding of neuronal development and help develop regenerative stem cell therapies for neurodegenerative diseases. Traditionally, reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence (IF) staining have been widely used to investigate stem cell differentiation; however, their limitations include endpoint analysis, invasive nature of monitoring, and lack of single-cell-level resolution. Several limitations hamper current approaches to studying neural stem cell (NSC) differentiation.

Probing Nanotopography-Mediated Macrophage Polarization via Integrated Machine Learning and Combinatorial Biophysical Cue Mapping.

Inflammatory responses, leading to fibrosis and potential host rejection, significantly hinder the long-term success and widespread adoption of biomedical implants. The ability to control and investigated macrophage inflammatory responses at the implant-macrophage interface would be critical for reducing chronic inflammation and improving tissue integration. Nonetheless, the systematic investigation of how surface topography affects macrophage polarization is typically complicated by the restricted complexity of accessible nanostructures, difficulties in achieving exact control, and biased preselection of experimental parameters.

Developing MiR-133a Zipper Nanoparticles for Targeted Enhancement of Thermogenic Adipocyte Generation.

Existing delivery methods for RNAi therapeutics encounter challenges, including stability, specificity, and off-target effects, which restrict their clinical effectiveness. In this study, a novel miR-133a zipper nanoparticle (NP) system that integrates miRNA zipper technology with rolling circle transcription (RCT) to achieve targeted delivery and specific regulation of miR-133a in adipocytes, is presented. This innovative approach can greatly enhance the delivery and release of miR-133a zippers, increasing the expression of thermogenic genes and mitochondrial biogenesis.

Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions.

Central Nervous System (CNS) disorders represent a profound public health challenge that affects millions of people around the world. Diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and traumatic brain injury (TBI) exemplify the complexities and diversities that complicate their early detection and the development of effective treatments. Amid these challenges, the emergence of nanotechnology and extracellular vesicles (EVs) signals a new dawn for treating and diagnosing CNS ailments.

Magnetic Nanoparticle-Assisted Non-Viral CRISPR-Cas9 for Enhanced Genome Editing to Treat Rett Syndrome.

The CRISPR-Cas9 technology has the potential to revolutionize the treatment of various diseases, including Rett syndrome, by enabling the correction of genes or mutations in human patient cells. However, several challenges need to be addressed before its widespread clinical application. These challenges include the low delivery efficiencies to target cells, the actual efficiency of the genome-editing process, and the precision with which the CRISPR-Cas system operates.

Enhancing CAR Macrophage Efferocytosis Via Surface Engineered Lipid Nanoparticles Targeting LXR Signaling.

The removal of dying cells, or efferocytosis, is an indispensable part of resolving inflammation. However, the inflammatory microenvironment of the atherosclerotic plaque frequently affects the biology of both apoptotic cells and resident phagocytes, rendering efferocytosis dysfunctional. To overcome this problem, a chimeric antigen receptor (CAR) macrophage that can target and engulf phagocytosis-resistant apoptotic cells expressing CD47 is developed.

Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo self-assembly composed of azobenzene derivatives (Azo) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces -Azo-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly.

Effective Modulation of Inflammation and Oxidative Stress for Enhanced Regeneration of Intervertebral Discs Using 3D Porous Hybrid Protein Nanoscaffold.

Degeneration of fibrocartilaginous tissues is often associated with complex pro-inflammatory factors. These include reactive oxygen species (ROS), cell-free nucleic acids (cf-NAs), and epigenetic changes in immune cells. To effectively control this complex inflammatory signaling, it developed an all-in-one nanoscaffold-based 3D porous hybrid protein (3D-PHP) self-therapeutic strategy for treating intervertebral disc (IVD) degeneration.

Nanotechnology Approaches for Prevention and Treatment of Chemotherapy-Induced Neurotoxicity, Neuropathy, and Cardiomyopathy in Breast and Ovarian Cancer Survivors.

Nanotechnology has emerged as a promising approach for the targeted delivery of therapeutic agents while improving their efficacy and safety. As a result, nanomaterial development for the selective targeting of cancers, with the possibility of treating off-target, detrimental sequelae caused by chemotherapy, is an important area of research. Breast and ovarian cancer are among the most common cancer types in women, and chemotherapy is an essential treatment modality for these diseases.

The effect of Nano-liposomal sodium nitrite on smooth muscle cell growth in a tissue-engineered small-diameter vascular graft.

Background: Nitric oxide is a chemical agent produced by endothelial cells in a healthy blood vessel, inhibiting the overgrowth of vascular smooth muscle cells and regulating vessel tone. Liposomes are biocompatible and biodegradable drug carriers with a similar structure to cell bilayer phospholipid membrane that can be used as useful nitric oxide carriers in vascular grafts.

Method: Using a custom-designed apparatus, the sheep carotid arteries were decellularized while still maintaining important components of the vascular extracellular matrix (ECM), allowing them to be used as small-diameter vascular grafts.

Development of a Nanohybrid Peptide Hydrogel for Enhanced Intervertebral Disc Repair and Regeneration.

Effective therapeutic approaches to overcome the heterogeneous pro-inflammatory and inhibitory extracellular matrix (ECM) microenvironment are urgently needed to achieve robust structural and functional repair of severely wounded fibrocartilaginous tissues. Herein we developed a dynamic and multifunctional nanohybrid peptide hydrogel (NHPH) through hierarchical self-assembly of peptide amphiphile modified with biodegradable two-dimensional nanomaterials with enzyme-like functions. NHPH is not only injectable, biocompatible, and biodegradable but also therapeutic by catalyzing the scavenging of pro-inflammatory reactive oxygen species and promoting ECM remodeling.

A novel co-culture assay to evaluate the effects of sympathetic innervation on vascular smooth muscle differentiation.

Dedifferentiation of vascular smooth muscle cells (VSMCs) from a functional phenotype to an inverse synthetic phenotype is a symptom of cardiovascular disorders, such as atherosclerosis and hypertension. The sympathetic nervous system (SNS) is an essential regulator of the differentiation of vascular smooth muscle cells (VSMCs). In addition, numerous studies suggest that SNS also stimulates VSMCs to retain their contractile phenotype.

Nanoparticle-Based Artificial Mitochondrial DNA Transcription Regulator: .

The growing knowledge of the links between aberrant mitochondrial gene transcription and human diseases necessitates both an effective and dynamic approach to control mitochondrial DNA (mtDNA) transcription. To address this challenge, we developed a nanoparticle-based synthetic mitochondrial transcription regulator (). provides great colloidal stability, excellent biocompatibility, efficient cell uptake, and selective mitochondria targeting and can be monitored in live cells using near-infrared fluorescence.

Injectable bioorthogonal hydrogel (BIOGEL) accelerates tissue regeneration in degenerated intervertebral discs.

Intervertebral disc (IVD) degeneration is a leading cause of back pain and precursor to more severe conditions, including disc herniation and spinal stenosis. While traditional growth factor therapies (e.g.

Advanced theragnostics for the central nervous system (CNS) and neurological disorders using functional inorganic nanomaterials.

Various types of inorganic nanomaterials are capable of diagnostic biomarker detection and the therapeutic delivery of a disease or inflammatory modulating agent. Those multi-functional nanomaterials have been utilized to treat neurodegenerative diseases and central nervous system (CNS) injuries in an effective and personalized manner. Even though many nanomaterials can deliver a payload and detect a biomarker of interest, only a few studies have yet to fully utilize this combined strategy to its full potential.

Structurally Defined Water-Soluble Metallofullerene Derivatives towards Biomedical Applications.

Endohedral metallofullerenes (EMFs) are excellent carriers of rare-earth element (REE) ions in biomedical applications because they preclude the release of toxic metal ions. However, existing approaches to synthesize water-soluble EMF derivatives yield mixtures that inhibit precise drug design. Here we report the synthesis of metallobuckytrio (MBT), a three-buckyball system, as a modular platform to develop structurally defined water-soluble EMF derivatives with ligands by choice.

Photoswitchable Microgels for Dynamic Macrophage Modulation.

Dynamic manipulation of supramolecular self-assembled structures is achieved irreversibly or under non-physiological conditions, thereby limiting their biomedical, environmental, and catalysis applicability. In this study, microgels composed of azobenzene derivatives stacked via π-cation and π-π interactions are developed that are electrostatically stabilized with Arg-Gly-Asp (RGD)-bearing anionic polymers. Lateral swelling of RGD-bearing microgels occurs via cis-azobenzene formation mediated by near-infrared-light-upconverted ultraviolet light, which disrupts intermolecular interactions on the visible-light-absorbing upconversion-nanoparticle-coated materials.