Biology subjects

Delporte, C.

Publications and source records attributed to Delporte, C..

3 recordsLinked to original sources

bioRxiv2026

A Protease-Cleavable iNOS-Inhibitor Polymeric Prodrug Designed for Controlled Modulation of Nitric Oxide

Inducible nitric oxide synthase (iNOS) is frequently overexpressed in inflammatory disorders and solid tumors, where sustained nitric oxide (NO) production promotes angiogenesis, tumor progression, and resistance to therapy. Despite promising preclinical results, the clinical translation of iNOS inhibitors remains limited by poor tumor selectivity, rapid systemic clearance, and off-target toxicities. To address these challenges, we developed a protease-responsive polymeric iNOS-inhibiting prodrug (ProCIP) designed for localized activation within protease-rich pathological microenvironments. ProCIP was synthesized from poly(ethylene glycol)-poly(L-glutamate) and functionalized with amidine-based iNOS inhibitory moieties. The resulting cationic polymer readily formed nanoscale polyionic complexes with anionic polymers or molecules. In cell-free assays, enzymatic activation of ProCIP resulted in a significant reduction in iNOS activity, whereas non-activated nanoparticles showed minimal inhibition. Cellular studies confirmed efficient nanoparticle uptake by RAW264.7 macrophages and revealed a significant reduction in intracellular NO levels in lipopolysaccharide-stimulated cells. These findings demonstrate that ProCIP enables protease-triggered iNOS inhibition and localized NO regulation, offering a promising strategy for improving the safety and efficacy of iNOS-targeted therapies in cancer and other inflammatory diseases.

pharmacology and toxicology↗

bioRxiv2026

Controlled delivery of iNOS antagonist, 1400W, for synergistic breast cancer therapy

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks effective targeted therapies and is frequently associated with chemotherapy resistance and immunosuppression. Inducible nitric oxide synthase (iNOS) is overexpressed in breast cancer and has been strongly correlated with poor clinical outcomes, owing to its role in promoting tumor progression, invasiveness, and resistance to therapy. Although highly selective iNOS inhibitors such as N-(3-(Aminomethyl)benzyl)acetamidine (1400W) exhibit considerable therapeutic promise, their clinical translation has been hindered by unfavorable pharmacokinetic properties. To overcome these limitations, we developed a pH-responsive nanoscale formulation based on Schiff base conjugation between 1400W and oxidized PEGylated alginate (OPA), in combination with ionic interactions. The resulting nanoparticles (NPs) exhibited efficient release of 1400W under acidic conditions and effectively suppressed nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. While the NPs alone did not induce significant cytotoxicity, they synergistically enhanced the anticancer efficacy of paclitaxel (PTX) in MDA-MB-231 TNBC cells, significantly inhibiting cell viability and migration. In addition, the NP-PTX combination markedly reduced endothelial tube formation in HUVECs, compared to PTX alone indicating potentiation of the anti-angiogenic activity of PTX. In conclusion, the pH-responsive NPs enables effective modulation of NO signaling and enhances the therapeutic activity of PTX in TNBC cells. These findings support the potential of iNOS-targeted nanomedicine as an adjuvant strategy for TNBC treatment and warrant further investigation using in vivo models to evaluate pharmacokinetics, tumor accumulation, and antitumor efficacy of the NPs.

pharmacology and toxicology↗

bioRxiv2025

Phosphate Limitation Modulates Vibrio cholerae Outer Membrane Vesicle Formation, Composition and Toxicity

Vibrio cholerae inhabits phosphorus-poor aquatic environments and host intestine, where it expresses genes regulated by the PhoB/PhoR two-component system in response to inorganic phosphate (Pi) limitation. Like other Gram-negative bacteria, V. cholerae releases outer membrane vesicles (OMVs), which carry proteins, lipids, and nucleic acids that contribute to adaptation, survival, and pathogenesis. Here, we investigated how Pi availability affects OMV production, composition, and toxicity in the pandemic strain N16961 and its {Delta}phoB mutant. Using transmission electron microscopy, atomic force microscopy, and nanoparticle tracking analysis, we show that OMV size remains constant ([~]140 nm) across conditions, but production is significantly increased under Pi limitation in a PhoB-dependent manner. Proteomic and lipidomic analyses revealed selective packaging of PhoB-regulated proteins involved in phosphate metabolism, stress response, carbon metabolism, and toxicity, as well as enrichment in phosphorus-free ornithine lipids under low Pi. Functional assays in Galleria mellonella demonstrated that OMVs from N16961 under Pi limitation are highly toxic, whereas OMVs from high-Pi or {Delta}phoB cultures exhibit minimal lethality. Our findings indicate that phosphate limitation acts as an environmental cue that shapes OMV composition, enhancing both bacterial survival and pathogenic potential. This study highlights OMVs as dynamic vehicles integrating adaptation to low Pi concentration, stress adaptation, and toxicity in V. cholerae.

microbiology↗