Multifunctional Boron-based 2D Nanoplatforms Ameliorate Severe Respiratory Inflammation by Targeting Multiple Inflammatory Mediators.

Effective management of serious respiratory diseases, such as asthma and recalcitrant rhinitis, remains a global challenge. Here, it is shown that induced sputum supernatants (ISS) from patients with asthma contain higher levels of cell-free DNA (cfDNA) compared to that of healthy volunteers. Although cfDNA scavenging strategies have been developed for inflammation modulation in previous studies, this fall short in clinical settings due to the excessive neutrophil extracellular trap (NET) formation, reactive oxygen and nitrogen species (RONS) and bacterial infections in injured airway tissues.

Intranasal PAMAM-G3 scavenges cell-free DNA attenuating the allergic airway inflammation.

Allergic airway inflammation (AAI), including allergic rhinitis (AR) and allergic asthma, is driven by epithelial barrier dysfunction and type 2 inflammation. However, the underlying mechanism remains uncertain and available treatments are constrained. Consequently, we aim to explore the role of cell-free DNA (cfDNA) in AAI and assess the potential alleviating effects of cationic polymers (CPs) through cfDNA elimination.

Inhibitory effects of black phosphorus nanosheets on tumor cell proliferation through downregulation of ADIPOQ and downstream signaling pathways.

Exposure to environmental pollutants, including nanomaterials, has a significant impact on tumor progression. The increased demand for black phosphorus nanosheets (BPNSs), driven by their exceptional properties, raises concerns about potential environmental contamination. Assessing their toxicity on tumor growth is essential.

Tackling Severe Neutrophilic Inflammation in Airway Disorders with Functionalized Nanosheets.

Severe airway inflammatory disorders impose a significant societal burden, and the available treatments are unsatisfactory. High levels of neutrophil extracellular trap (NET) and cell-free DNA (cfDNA) were detected in the inflammatory microenvironment of these diseases, which are closely associated with persistent uncontrolled neutrophilic inflammation. Although DNase has proven to be effective in mitigating neutrophilic airway inflammation in mice by reducing cfDNA and NET levels, its clinical use is hindered by severe side effects.

Comparative Analysis of Nucleic Acid-Binding Polymers as Potential Anti-Inflammatory Nanocarriers.

Conventionally, nanocarriers are used to regulate the controlled release of therapeutic payloads. Increasingly, they can also be designed to have an intrinsic therapeutic effect. For example, a positively charged nanocarrier can bind damage-associated molecular patterns, inhibiting toll-like receptor (TLR) pathway activation and thus modulating inflammation.

Efficient skin interactions of graphene derivatives: challenge, opportunity or both?

Interactions between graphene, with its wide deployment in consumer products, and skin, the body's largest organ and first barrier, are highly relevant with respect to toxicology and dermal delivery. In this work, interaction of polyglycerol-functionalized graphene sheets, with 200 nm average lateral size and different surface charges, and human skin was studied and their potential as topical delivery systems were investigated. While neutral graphene sheets showed no significant skin interaction, their positively and negatively charged counterparts interacted with the skin, remaining in the stratum corneum.

Construction of CpG Delivery Nanoplatforms by Functionalized MoS Nanosheets for Boosting Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.

Despite the promising achievements of immune checkpoint blockade (ICB) therapy for tumor treatment, its therapeutic effect against solid tumors is limited due to the suppressed tumor immune microenvironment (TIME). Herein, a series of polyethyleneimine (Mw = 0.8k, PEI )-covered MoS nanosheets with different sizes and charge densities are synthesized, and the CpG, a toll-like receptor-9 agonist, is enveloped to construct nanoplatforms for the treatment of head and neck squamous cell carcinoma (HNSCC).

Polyglycerol-Amine Covered Nanosheets Target Cell-Free DNA to Attenuate Acute Kidney Injury.

Increased levels of circulating cell-free DNA (cfDNA) are associated with poor clinical outcomes in patients with acute kidney injury (AKI). Scavenging cfDNA by nanomaterials is regarded as a promising remedy for cfDNA-associated diseases, but a nanomaterial-based cfDNA scavenging strategy has not yet been reported for AKI treatment. Herein, polyglycerol-amine (PGA)-covered MoS nanosheets with suitable size are synthesized to bind negatively charged cfDNA in vitro, in vivo and ex vivo models.

Screening of Tumor Antigens and Construction of Immune Subtypes for mRNA Vaccine Development in Head and Neck Squamous Cell Carcinoma.

Background: A growing number of clinical studies have confirmed that mRNA vaccines are effective in the treatment of malignant tumors; however, their efficacy in head and neck squamous cell carcinoma (HNSCC) has not been determined. This study aimed to identify the potential antigens of HNSCC for mRNA vaccine development and further distinguish the immune subtypes of HNSCC to select suitable patients for vaccination.

Methods: We obtained gene expression profiles and corresponding clinical information of HNSCC from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA).

Design of therapeutic biomaterials to control inflammation.

Inflammation plays an important role in the response to danger signals arising from damage to our body and in restoring homeostasis. Dysregulated inflammatory responses occur in many diseases, including cancer, sepsis and autoimmunity. The efficacy of anti-inflammatory drugs, developed for the treatment of dysregulated inflammation, can be potentiated using biomaterials, by improving the bioavailability of drugs and by reducing side effects.

A Versatile and Robust Platform for the Scalable Manufacture of Biomimetic Nanovaccines.

Biomimetic strategies are useful for designing potent vaccines. Decorating a nanoparticulate adjuvant with cell membrane fragments as the antigen-presenting source exemplifies, such as a promising strategy. For translation, a standardizable, consistent, and scalable approach for coating nanoadjuvant with the cell membrane is important.

Dose-Dependent Carbon-Dot-Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism.

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized.

Biomimetic Diselenide-Bridged Mesoporous Organosilica Nanoparticles as an X-ray-Responsive Biodegradable Carrier for Chemo-Immunotherapy.

Chemotherapy causes off-target toxicity and is often ineffective against solid tumors. Targeted and on-demand release of chemotherapeutics remains a challenge. Here, cancer-cell-membrane-coated mesoporous organosilica nanoparticles (MONs) containing X-ray- and reactive oxygen species (ROS)-responsive diselenide bonds for controlled release of doxorubicin (DOX) at tumor sites are developed.

Janus Nanobullets Combine Photodynamic Therapy and Magnetic Hyperthermia to Potentiate Synergetic Anti-Metastatic Immunotherapy.

Photodynamic therapy (PDT) is clinically promising in destructing primary tumors but ineffective against distant metastases. This study reports the use of immunogenic nanoparticles mediated combination of PDT and magnetic hyperthermia to synergistically augment the anti-metastatic efficacy of immunotherapy. Janus nanobullets integrating chlorine e6 (Ce6) loaded, disulfide-bridged mesoporous organosilica bodies with magnetic heads (M-MONs@Ce6) are tailored for redox/pH-triggered photosensitizer release accompanying their matrix degradation.

Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein.

Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven.

Positively Charged Nanoaggregates Based on Zwitterionic Pillar[5]arene that Combat Planktonic Bacteria and Disrupt Biofilms.

Bacterial biofilms are difficult to eradicate because they are less susceptible to antibiotics and more easily develop resistance. Therefore, there is an urgent need for new materials that can combat planktonic bacteria and disrupt established biofilms. To tackle this challenge, we design a multifunctional zwitterionic pillar[5]arene, which can self-assemble into weakly positively charged nanoaggregates that exhibit antibacterial activity against Gram-negative Escherichia coli (DH5α) and Gram-positive Staphylococcus aureus (SH1000) bacterial strains in solution.

Directed Graphene-Based Nanoplatforms for Hyperthermia: Overcoming Multiple Drug Resistance.

Multidrug resistance (MDR), which leads tumors resistance to traditional anticancer drugs, can cause the failure of chemotherapy treatments. Herein, we present a new way to overcome this problem using smart multifunctional graphene-based drug delivery systems which can target subcellular organelles and show synergistic hyperthermia and chemotherapy. Mitochondria-targeting ligands are conjugated onto the doxorubicin-loaded, polyglycerol-covered nanographene sheets to actively accumulate them inside the mitochondria after charge-mediated cellular internalization.

Multivalent Interactions between 2D Nanomaterials and Biointerfaces.

2D nanomaterials, particularly graphene, offer many fascinating physicochemical properties that have generated exciting visions of future biological applications. In order to capitalize on the potential of 2D nanomaterials in this field, a full understanding of their interactions with biointerfaces is crucial. The uptake pathways, toxicity, long-term fate of 2D nanomaterials in biological systems, and their interactions with the living systems are fundamental questions that must be understood.

Functionalized graphene sheets for intracellular controlled release of therapeutic agents.

Since therapeutic agents target specific compartments inside the cells, their efficiency depends on their intracellular release from drug delivery systems (DDS). However, control over the intracellular release of therapeutic agents is a challenging issue and can only be achieved by governing their interactions with the DDS. In this work, polyglycerol amine- and polyglycerol sulfate-functionalized graphene sheets as positively and negatively charged 2D nanomaterials with 150 nm lateral size were used to deliver and control the release of doxorubicin (DOX) inside cells.

Construction of Functional Coatings with Durable and Broad-Spectrum Antibacterial Potential Based on Mussel-Inspired Dendritic Polyglycerol and in Situ-Formed Copper Nanoparticles.

A novel surface coating with durable broad-spectrum antibacterial ability was prepared based on mussel-inspired dendritic polyglycerol (MI-dPG) embedded with copper nanoparticles (Cu NPs). The functional surface coating is fabricated via a facile dip-coating process followed by in situ reduction of copper ions with a MI-dPG coating to introduce Cu NPs into the coating matrix. This coating has been demonstrated to possess efficient long-term antibacterial properties against Escherichia coli (E.

Bioreducible Peptide-Dendrimeric Nanogels with Abundant Expanded Voids for Efficient Drug Entrapment and Delivery.

Dendrimer-based nanoplatforms have exhibited wide prospects in the field of nanomedicine for drug delivery, without great success due to many predicaments of cytotoxicity, high cost, and low yield. In this work, we report a feasible strategy on dynamic cross-linkings of low-generation peptide dendrimers into bioreducible nanogels for efficient drug controlled release. With a facile fabrication, the disulfide cross-linking of biocompatible peptide dendrimers successfully possess well-defined and stable nanostructures with abundant expanded voids for efficient molecular encapsulation.

pH-degradable PVA-based nanogels via photo-crosslinking of thermo-preinduced nanoaggregates for controlled drug delivery.

pH-Degradable PVA nanogels, which are prepared by photo-crosslinking thermo-preinduced PVA nanoaggregates in water without any surfactants or toxic organic solvents, are used for intracellular PTX release and anticancer treatment. These nanogels fast degraded at mildly acidic conditions with a pH-triggered PTX release, and the degradation products are only native PVA and poly(hydroxyethyl acrylate) (PHEA) as well as acetaldehyde without any toxic byproducts. The nanogel sizes could be tailored by different temperatures during the crosslinking process.