Biology subjects

Halberg, N.

Publications and source records attributed to Halberg, N..

6 recordsLinked to original sources

bioRxiv2026

Injectable Electrospun Hydrogel with Antimicrobial, pH Sensing Nanoparticles for Local Infection Control and Monitoring

Most antimicrobial drug candidates currently in development are derivatives of established antibiotic classes. In contrast, antimicrobial heteroatom-doped carbon quantum dot (COD) nanoparticles vastly differ from their chemical antibiotic counterparts and exhibit potent antibacterial activity and favourable biocompatibility, representing a promising alternative strategy, particularly for topical applications. Here, we report the incorporation of cobalt-doped carbon quantum dots (Co-CODs) into injectable, biocompatible hydrogels capable of both sensing pH and eliminating bacteria. Ultrasmall Co-CODs demonstrated broad-spectrum activity against gram-positive Methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Pseudomonas aeruginosa (PAO1), mediated by membrane hyperpolarisation and reactive oxygen species (ROS) induced membrane damage. The particles showed negligible effect on primary fibroblast and endothelial cell viability at concentrations that were bactericidal to MRSA. Polymeric hydrogels were fabricated via electrospinning of chitosan, polyvinylpyrrolidone (PVP), and polyvinyl alcohol (PVA) polymer blends incorporating Co-COD and pH-responsive HPTS particles. This approach provided accurate measurement of environmental pH within the physiological range observed across healthy and chronic wounds. In vivo, the injectable hydrogels exhibited robust antimicrobial efficacy against MRSA without impairing wound closure relative to untreated controls, while also reducing inflammatory immune responses in infected tissues. Collectively, these findings demonstrate the potential of ultrasmall metal-doped CODs for infection control and their integration into 3D matrices as multifunctional theragnostic platforms. ToC (<60 words describe the main results)Ultrasmall antimicrobial carbon nanoparticles were incorporated into polymeric hydrogels containing a pH-responsive probe. This platform enabled detection across a physiologically relevant pH range of 5.0-6.5, spanning conditions associated with both healthy healing and chronically infected wounds. The hydrogel demonstrated strong antibacterial activity by generating damaging reactive oxygen species, and, in mice, effectively controlled infection while reducing pro-inflammatory immune responses. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/736887v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1a52b32org.highwire.dtl.DTLVardef@b6eed2org.highwire.dtl.DTLVardef@1f94143org.highwire.dtl.DTLVardef@12b9ff3_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOScheme 1:C_FLOATNO Antimicrobial nanoparticle-doped hydrogel glows in alkaline wound conditions which are representative of chronic infections. Once in the wound bed, the hydrogel removes all MRSA infection, reducing inflammatory macrophage (iNOS) and neutrophil (MPO) populations, and restores healthy wound collagen deposition. C_FIG

bioengineering↗

bioRxiv2024

Acetic acid induces osmotic imbalances in drug-resistant bacteria synergistically enhancing cobalt-doped carbon quantum dots bactericidal efficiency

When pathogenic bacteria colonise a wound, they can create an alkaline ecological niche which selects for their survival by creating an inflammatory environment which restricts healthy wound healing to proceed. To aid healing, wound acidification has been exploited to disrupt this process and stimulate fibroblast growth, increase wound oxygen concentrations, minimise proteolytic activity and re-stimulate the host immune system. Within this study, we have developed unique cobalt doped carbon quantum dot nanoparticles which work together with mild acetic acid creating a potent synergistic antimicrobial therapy. The acidic environment alters the osmotic balance of microorganisms forcing them to swell and speed up the internalisation of the ultra-small particles. The particles hyperpolarise the bacterial membranes and generate damaging peroxidase species resulting in cellular lysis. In mice, cobalt doped carbon quantum dots remove MRSA infection while allowing wounds to heal at equivalent rates to uninfected wounds. This work demonstrates how synergistic antimicrobial treatment strategies can be successfully used to combat antimicrobial resistant infections.

microbiology↗

bioRxiv2024

Interactions between neutrophils and macrophages harboring gram-negative bacteria promote obesity-associated breast cancer

Obesity promotes a more aggressive breast cancer phenotype. Through spatial and single-cell-based analysis of hormone receptor-negative breast cancers, we identify a subset of tumor-associated neutrophils (TANs) positive for granzyme B (GZMB) enriched in the tumor microenvironment of obese patients. In breast tumors evolved in obese environments, TANs are in proximity of M2 polarized macrophages containing lipopolysaccharides (LPS) from gram-negative bacteria. Pyroptosis of macrophages releases bacterial LPS, activating local GZMB+ TANs. This induces release of the S100 family member S100A8 that promotes tumor progression. In sum, we describe an obesity associated cellular network of cancer cells, neutrophils and M2 polarized macrophages that promotes tumor growth.

cancer biology↗

bioRxiv2020

High dimensional immunotyping of the obese tumor microenvironment reveals model specific adaptation

Obesity is a disease characterized by chronic low-grade systemic inflammation and has been causally linked to the development of 13 cancer types. Several studies have been undertaken to determine if tumors evolving in obese environments adapt differential interactions with immune cells and if this can be connected to disease outcome. Most of these studies have been limited to single cell lines and tumor models and analysis of limited immune cell populations. Given the multicellular complexity of the immune system and its dysregulation in obesity, we applied high-dimensional suspension mass cytometry to investigate how obesity affects tumor immunity. We used a 36-marker immune-focused mass cytometry panel to interrogate the immune landscape of orthotopic syngeneic mouse models of pancreatic and breast cancer. Unanchored batch correction was implemented to enable simultaneous analysis of tumor cohorts to uncover the immunotypes of each cancer model and reveal remarkably model-specific immune regulation. In the E0771 breast cancer model, we demonstrate an important link to obesity with an increase in two T cell suppressive cell types and a decrease in CD8 T-cells.

cancer biology↗

bioRxiv2020

C/EBPB-dependent Adaptation to Palmitic Acid Promotes Stemness in Hormone Receptor Negative Breast Cancer

Epidemiological studies have established a positive association between obesity and the incidence of postmenopausal breast cancer. Moreover, it is known that obesity promotes stem cell-like properties of breast cancer cells. However, the cancer cell-autonomous mechanisms underlying this correlation are not well defined. Here we demonstrate that obesity-associated tumor formation is driven by cellular adaptation rather than expansion of pre-existing clones within the cancer cell population. While there is no correlation with specific mutations, cellular adaptation to obesity is governed by palmitic acid (PA) and leads to enhanced tumor formation capacity of breast cancer cells. This process is governed epigenetically through increased chromatin occupancy of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPB). Obesity-induced epigenetic activation of C/EBPB regulates cancer stem-like properties by modulating the expression of key downstream regulators including CLDN1 and LCN2. Collectively, our findings demonstrate that obesity drives cellular adaptation to PA drives tumor initiation in the obese setting through activation of a C/EBPB dependent transcriptional network. SignificanceCellular adaptation to obesity-induced palmitic acid drives tumor initiation through activation of a C/EBPB-dependent transcriptional network. This highlights a cell-autonomous mechanistic connection between obesity and postmenopausal hormone receptor negative breast cancer.

cancer biology↗

bioRxiv2019

Golgi-localized PAQR4 mediates Anti-apoptotic Ceramidase Activity in Breast Cancer

The metabolic network of sphingolipids plays important roles in cancer biology. Prominent sphingolipids include ceramides and sphingosine-1-phosphate that regulate multiple aspects of growth, apoptosis and cellular signaling. Although many significant enzymatic regulators of the sphingolipid pathway have been described in detail, the list is currently incomplete. Here, we applied a systemic approach to identify and molecularly define progestin and adipoQ receptor family member IV (PAQR4) as a Golgi-localized ceramidase. We find PAQR4 to be [~]5 fold upregulated in breast cancer compared to matched control tissue and that its overexpression correlate with disease-specific survival rates in breast cancer. PAQR4 is a seven transmembrane protein, and depletion of PAQR4 leads to cellular apoptosis through accumulation of ceramides. Our findings establish PAQR4 as Golgi-localized ceramidase required for cellular growth in breast cancer.

cancer biology↗