A Dual-Pronged Hafnia–Prodrug–Lipid Nanoplatform Coupling Radiosensitization and DNA Homologous Recombination Inhibition

ACS Nano Medicine · 2026-04-13

Emerging nanomedicine strategies have established clinical translation and the ability to offset conventional therapeutic challenges. This study aimed to report the development and analysis of a nanoscale material that functioned as both a high-Z radiosensitizer and a prodrug delivery system. In this study, a nanoscale platform using two complementary radiosensitizing mechanisms was designed and developed to overcome nonspecific toxicity, which is a challenge in both chemotherapy and radiotherapy. High-Z physical radiosensitization was coupled with the inhibition of a critical DNA double-strand break repair mechanism, homologous recombination, through a lipid nanoparticle decorated with ultrasmall Hafnia nanoparticles and loaded with an amphiphilic prodrug. In vitro and in vivo studies demonstrated significant enhancement of therapeutic effects, cell killing, or tumor regression, respectively, versus radiation alone. These results support the use of this combination system as a practical strategy for maintaining treatment efficacy at modest doses of radiation and offset associated adverse effects.

Exosome–niosome hybrid oxygen carrier for protection against acetaminophen-induced acute liver injury

Biomaterials Science · 2026-01-01

. Furthermore, histological analysis revealed protective effects of ENh-OCs against centrilobular necrosis and excessive immune-infiltration. We propose that the novel oxygen nanocarrier platform introduced here might act as a protective agent against APAP-induced ALI.

A review of spontaneous bone metastases in domestic and laboratory animals

Journal of bone oncology · 2026-04-22

• Bone metastases cause significant morbidity and death in cancer patients. • Animals with naturally occurring cancers are unique models for cancer research • This review covers the natural history of bone metastases in non-human species. Bone metastases cause significant morbidity and ultimately death in some human cancer patients. Although experimental animal models of skeletal metastases have been invaluable for investigating the molecular mechanisms of cancer progression and growth in bones, few of these models recapitulate the heterogeneous nature of bone metastases observed in humans. Animals with naturally occurring cancers have been proposed as ideal and unique models for human cancer research. From this, understanding the incidence, histologic features, clinical presentation, and response to therapy of spontaneous bone metastases in animals with different cancers will help with animal model selection and translational experiments on bone metastasis. This review provides an overview of the natural history of spontaneous bone metastases that occur in animals with spontaneous cancer. The review focuses on companion animals (dogs and cats) and includes rodents and other animal species. The similarities and differences compared to human bone metastases are highlighted, permitting a valuable resource for future skeletal metastasis modeling and therapeutic discovery.

Loss of Mast cells and histaminergic signaling link diet to platelet-mediated NETosis and mammary cancer recurrence

bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-15

ABSTRACT Breast cancer recurrence remains a clinical challenge. The period after the treatment of the primary tumor while cancer cells that evaded initial treatment lay dormant, provides a unique window of opportunity for interventions to prevent recurrence. Specific modifiable factors such as consumption of high fat diets or elevated circulating cholesterol are associated with decreased time to recurrence. Mechanistically, oxidized cholesterol and lipid species have been implicated in the regulation of the tumor microenvironment. This suggests that consumption of food prepared under oxidizing conditions such as pan-frying, may be an underappreciated risk. Using murine models of mammary cancer dormancy, we found that a diet enriched with fat from fried, cured bacon (cfBF) decreased dormancy latency times. Resulting lesions had fewer mast cells (MCs). Loss of MCs alone resulted in reemergence from dormancy. Elevated expression of a MC gene signature in breast tumors was associated with improved progression free and overall survival, highlighting the human relevance of these findings. MCs are a major source of tissue histamine, and lesions from mice fed cfBF had decreased concentrations. Importantly, antagonists of the histamine receptor 2 (H 2 R) sparked reemergence from dormancy. H 2 R antagonists are over-the-counter drugs are taken to alleviate gastroesophageal reflux disease. Chronic treatment of mice with H 2 R-antagonists sensitized platelets towards activation and crosstalk with neutrophils, and subsequent formation of neutrophil extracellular traps (NETs). The loss of platelet or NETosis activity mitigated the H 2 R-antagonist stimulated reemergence from dormancy. Therefore, we establish a novel metastatic axis which links diet to recurrence via MCs, histaminergic signaling and NETosis: Diet -- MC -- H 2 R -- ( decreased ) Platelet Activity -- ( decreased ) Neutrophil-NETosis -- ( decreased ) Reemergence from Dormancy. Our data reveal several potential intervention strategies: lifestyle, MC stabilization, histaminergic signaling, and neutrophil and platelet activity.

Osteosarcoma

2026-01-01

Supplementary Figure S1 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas

2025-11-25

<p>Patient tumor images and cohorts</p>

Supplementary Table S1 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas

2025-11-25

<p>Protein sequences of canine cytokine fusion proteins</p>

Supplementary Figure S4 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas

2025-11-25

<p>IFN-γ and IL-10 individual replicates from Milliplex, sarcoma patients</p>

Supplementary Figure S7 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas

2025-11-25

<p>Pathway scores from mouse Nanostring nSolver analysis</p>

1195 Evaluation of alum-anchored IL-12 (JEN-101) immunotherapy in canine melanoma: safety and efficacy across weight-based and tumor volume dosing strategies

Regular and Young Investigator Award Abstracts · 2025-11-01