Long-Lasting, Transparent Antibacterial Shield: A Durable, Broad-Spectrum Anti-Bacterial, Non-Cytotoxic, Transparent Nanocoating for Extended Wear Contact Lenses.

The increasing incidence of serious bacterial keratitis, a sight-threatening condition often exacerbated by inadequate contact lens (CLs) care, highlights the need for innovative protective technology. This study introduces a long-lasting antibacterial, non-cytotoxic, transparent nanocoating for CLs via a solvent-free polymer deposition method, aiming to prevent bacterial keratitis. The nanocoating comprises stacked polymer films, with poly(dimethylaminomethyl styrene-co-ethylene glycol dimethacrylate) (pDE) as a biocompatible, antibacterial layer atop poly(2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane) (pV4D4) as an adhesion-promoting layer.

Could artificial intelligence revolutionize the development of nanovectors for gene therapy and mRNA vaccines?

Gene therapy enables the introduction of nucleic acids like DNA and RNA into host cells, and is expected to revolutionize the treatment of a wide range of diseases. This growth has been further accelerated by the discovery of CRISPR/Cas technology, which allows accurate genomic editing in a broad range of cells and organisms . Despite many advances in gene delivery and the development of various viral and non-viral gene delivery vectors, the lack of highly efficient non-viral systems with low cellular toxicity remains a challenge.

Deep learning-assisted sensitive detection of fentanyl using a bubbling-microchip.

Deep learning-enabled smartphone-based image processing has significant advantages in the development of point-of-care diagnostics. Conventionally, most deep-learning applications require task specific large scale expertly annotated datasets. Therefore, these algorithms are oftentimes limited only to applications that have large retrospective datasets available for network development.

Macrophage-Encapsulated Bioorthogonal Nanozymes for Targeting Cancer Cells.

Macrophages migrate to tumor sites by following chemoattractant gradients secreted by tumor cells, providing a truly active targeting strategy for cancer therapy. However, macrophage-based delivery faces challenges of cargo loading, control of release, and effects of the payload on the macrophage vehicle. We present a strategy that employs bioorthogonal "nanozymes" featuring transition metal catalysts (TMCs) to provide intracellular "factories" for the conversion of prodyes and prodrugs into imaging agents and chemotherapeutics.

Selective treatment of intracellular bacterial infections using host cell-targeted bioorthogonal nanozymes.

Intracellular bacterial infections are difficult to treat, and in the case of and related infections, can be life threatening. Antibiotic treatments for intracellular infections face challenges including cell penetration and intracellular degradation that both reduce antibiotic efficacy. Even when treatable, the increased dose of antibiotics required to counter infections can strongly impact the microbiome, compromising the native roles of beneficial non-pathogenic species.

SARS-CoV-2 RNA Detection by a Cellphone-Based Amplification-Free System with CRISPR/CAS-Dependent Enzymatic (CASCADE) Assay.

CRISPR (Clustered regularly interspaced short palindromic repeats)-based diagnostic technologies have emerged as a promising alternative to accelerate delivery of SARS-CoV-2 molecular detection at the point of need. However, efficient translation of CRISPR-diagnostic technologies to field application is still hampered by dependence on target amplification and by reliance on fluorescence-based results readout. Herein, an amplification-free CRISPR/Cas12a-based diagnostic technology for SARS-CoV-2 RNA detection is presented using a smartphone camera for results readout.

Nanodelivery vehicles induce remote biochemical changes in vivo.

Nanomaterial-based platforms are promising vehicles for the controlled delivery of therapeutics. For these systems to be both efficacious and safe, it is essential to understand where the carriers accumulate and to reveal the site-specific biochemical effects they produce in vivo. Here, a dual-mode mass spectrometry imaging (MSI) method is used to evaluate the distributions and biochemical effects of anti-TNF-α nanoparticle stabilized capsules (NPSCs) in mice.

High-content and high-throughput identification of macrophage polarization phenotypes.

Macrophages are plastic cells of the innate immune system that perform a wide range of immune- and homeostasis-related functions. Due to their plasticity, macrophages can polarize into a spectrum of activated phenotypes. Rapid identification of macrophage polarization states provides valuable information for drug discovery, toxicological screening, and immunotherapy evaluation.

Dual Mass Spectrometric Tissue Imaging of Nanocarrier Distributions and Their Biochemical Effects.

Nanomaterial-based drug delivery vehicles are able to deliver therapeutics in a controlled, targeted manner. Currently, however, there are limited analytical methods that can detect both nanomaterial distributions and their biochemical effects concurrently. In this study, we demonstrate that matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI) can be used together to obtain nanomaterial distributions and biochemical consequences.

In Vivo Editing of Macrophages through Systemic Delivery of CRISPR-Cas9-Ribonucleoprotein-Nanoparticle Nanoassemblies.

Macrophages are key effectors of host defense and metabolism, making them promising targets for transient genetic therapy. Gene editing through delivery of the Cas9-ribonucleoprotein (RNP) provides multiple advantages over gene delivery-based strategies for introducing CRISPR machinery to the cell. There are, however, significant physiological, cellular, and intracellular barriers to the effective delivery of the Cas9 protein and guide RNA (sgRNA) that have to date, restricted Cas9 protein-based approaches to local/topical delivery applications.

Macrophage activation by a substituted pyrimido[5,4-b]indole increases anti-cancer activity.

Immunotherapy has become a promising new approach for cancer treatment due to the immune system's ability to remove tumors in a safe and specific manner. Many tumors express anti-inflammatory factors that deactivate the local immune response or recruit peripheral macrophages into pro-tumor roles. Because of this, effective and specific ways of activating macrophages into anti-tumor phenotypes is highly desirable for immunotherapy purposes.

Nanocapsule-mediated cytosolic siRNA delivery for anti-inflammatory treatment.

The use of nanoparticle-stabilized nanocapsules for cytosolic siRNA delivery for immunomodulation in vitro and in vivo is reported. These NPSCs deliver siRNA directly to the cytosol of macrophages in vitro with concomitant knockdown of gene expression. In vivo studies showed directed delivery of NPSCs to the spleen, enabling gene silencing of macrophages, with preliminary studies showing 70% gene knockdown at a siRNA dose of 0.

Surface-Modified Macrophages Facilitate Tracking of Breast Cancer-Immune Interactions.

The immune system has been found to play key roles in cancer development and progression. Macrophages are typically considered to be pro-inflammatory cells but can also facilitate pro-oncogenic activities via associations with tumors and metastases. The study of macrophages and their interactions within the context of cancer microenvironments is stymied by the lack of a system to track them.

Harnessing Biology to Deliver Therapeutic and Imaging Entities via Cell-Based Methods.

The accumulation of therapeutic and imaging agents at sites of interest is critical to their efficacy. Similarly, off-target effects (especially toxicity) are a major liability for these entities. For this reason, the use of delivery vehicles to improve the distribution characteristics of bio-active agents has become ubiquitous in the field.

Effects of engineered nanoparticles on the innate immune system.

Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses.

Simultaneous cytosolic delivery of a chemotherapeutic and siRNA using nanoparticle-stabilized nanocapsules.

We report on nanoparticle-stabilized capsules (NPSCs) as a platform for the co-delivery of survivin-targeted siRNA and tamoxifen. These capsules feature an inner oil core that provides a carrier for tamoxifen, and is coated on the surface with positively charged nanoparticles self-assembled with siRNA. The multifaceted chemical nature of the NPSC system enables the simultaneous delivery of both payloads directly into the cytosol in vitro.

Chemically Engineered Nanoparticle-Protein Interface for Real-Time Cellular Oxidative Stress Monitoring.

A co-engineered nanoparticle/protein peroxide detector is created. This system features a gold nanoparticle functionalized with a galactose headgroup (AuNP-Gal) that reacts covalently with a boronate-modified green fluorescent protein (PB-GFP). Boronate acid-saccharide complexation between PB-GFP and AuNP-Gal affords a highly stable assembly.

Progress and perspective of inorganic nanoparticle-based siRNA delivery systems.

Introduction: Small interfering RNA (siRNA) is an effective method for regulating the expression of proteins, even "undruggable" ones that are nearly impossible to target through traditional small molecule therapeutics. Delivery to the cell and then to the cytosol is the primary requirement for realization of therapeutic potential of siRNA.

Areas Covered: We summarize recent advances in the design of inorganic nanoparticle with surface functionality and physicochemical properties engineered for siRNA delivery.

Promises and pitfalls of intracellular delivery of proteins.

The direct delivery of functional proteins into the cell cytosol is a key issue for protein therapy, with many current strategies resulting in endosomal entrapment. Protein delivery to the cytosol is challenging due to the high molecular weight and the polarity of therapeutic proteins. Here we review strategies for the delivery of proteins into cells, including cell-penetrating peptides, virus-like particles, supercharged proteins, nanocarriers, polymers, and nanoparticle-stabilized nanocapsules.

(1H-Imidazol-4-yl)methanol.

The title compound, C4H6N2O, displays two predominant hydrogen-bonding inter-actions in the crystal structure. The first is between the unprotonated imidazole N atom of one mol-ecule and the hy-droxy H atom of an adjacent mol-ecule. The second is between the hy-droxy O atom of one mol-ecule and the imidazole N-H group of a corresponding mol-ecule.