Biology subjects

Alimoradi, H.

Publications and source records attributed to Alimoradi, H..

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↗

bioRxiv2021

Enhanced keratin extraction from wool waste using a deep eutectic solvent

In this study, the solubilisation of waste coarse wool as a precursory step for the large scale valorisation of keratin was investigated using a green deep eutectic solvent (DES) based on L-cysteine and lactic acid. The investigation was undertaken via the response surface methodology and based on the Box-Behnken design for four process variables of temperature (70-110 {degrees}C), dissolution time (2-10 h), the mass of L-cysteine (0.5-2.5 g) in 20 mL of lactic acid, and wool load in the DES (0.2-0.6 g). The effect of variations in temperature was established to be the most significant process variable influencing keratin yield from waste coarse wool in the current work. An optimum keratin yield (93.77 wt.%) was obtained at the temperature of 105 {degrees}C, 8 h dissolution time, with 1.6 g L-cysteine in 20 mL of lactic acid using 0.5 g of wool. This study suggests L-cysteine and lactic acid as a green solvent with the potential to scale up keratin recovery from waste wool without significant destruction in the structure of the recovered keratin. HighlightsO_LIKeratin recovery from wool using deep eutectic solvent was assessed C_LIO_LIThe basis for the use of the new deep eutectic solvent was discussed C_LIO_LIThe effects of the process variables on keratin yield were explored C_LIO_LIKeratin recovered was optimised and characterised. C_LI

bioengineering↗