bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.11.04.621820

Potassium ferric oxalate nanoparticles prevent human blood clotting and thrombosis in a mouse model

Abstract

Blood clot creates occlusion in the veins and arteries, which leads to pernicious effects. Here, the anticoagulation properties of potassium ferric oxalate nanoparticles (KFeOx-NPs) in human blood were demonstrated for blood clot management. The mechanism involves the chelation of calcium ions from the blood by the oxalate present in the KFeOx-NPs. Various commercial assays were used to determine the clotting time for the KFeOx-NPs and identified the hindrance in activating factor XII in the intrinsic pathway. We used animal models to show toxicity and biodistribution profiles and determined the safety and efficacy. Intravenously injected KFeOx-NPs increased clotting time and thrombosis prevention in a mouse model confirmed by ultrasound and the power Doppler images. Coating catheters with KFeOx-NPs prevents clot formation with reduced protein attachment when incubated with blood, enhancing blood flow properties. In biological applications, KFeOx-NPs may improve the long-term prevention of blood clot formation and enhance the efficiency of medical devices. TOC O_FIG O_LINKSMALLFIG WIDTH=188 HEIGHT=200 SRC="FIGDIR/small/621820v1_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@1292afeorg.highwire.dtl.DTLVardef@1c5ba81org.highwire.dtl.DTLVardef@576f23org.highwire.dtl.DTLVardef@4186e9_HPS_FORMAT_FIGEXP M_FIG C_FIG PVP-stabilized novel potassium ferric oxalate nanoparticles were synthesized for the application of blood clot management and thrombosis prevention.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Yenurkar, D., Choudhary, A., Shrivastava, A., Pragya, P., Mandal, S., Soni, P., Pradhan, L., Singh, A., Sarkar, A., Mukherjee, S.. 2024-11-05. Potassium ferric oxalate nanoparticles prevent human blood clotting and thrombosis in a mouse model. https://doi.org/10.1101/2024.11.04.621820

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Autophagic flux is increased in peripheral blood mononuclear cells in atherosclerotic vascular disease and associates inversely with adverse cardiovascular events

Background: Autophagy is a homeostatic pathway supporting stress adaptation and is dysregulated in atherosclerosis. Its potential as a biomarker or therapeutic target in atherosclerotic vascular disease (ASVD) remains incompletely defined. We measured autophagic flux in peripheral blood mononuclear cells (PBMCs) from patients with peripheral arterial disease (PAD) or carotid stenosis (CS), compared with healthy controls, and explored clinical outcome associations. Methods: Ninety-four patients with PAD or CS and 19 healthy controls were studied. Autophagic flux was quantified from fresh blood using a validated ex vivo chloroquine inhibition ELISA measuring LC3BII accumulation. Major adverse cardiovascular events (MACE) and major adverse limb events (MALE) were ascertained over a median follow up of 828 days. Results: The ASVD cohort comprised claudication (n = 16), chronic limb threatening ischemia (CLTI; n = 49), and CS (n = 29). Autophagic flux was higher in ASVD than controls (mean 281.4 vs. 182.3 ng LC3BII/mg protein/h; p < 0.0001) and remained independently associated after multivariable adjustment. Within CLTI, concurrent infection was associated with lower flux (p = 0.001), approaching control levels (p = 0.327). In CLTI, higher flux quartiles were associated with lower MACE risk, most strongly for quartile 3 (hazard ratio 0.07 vs. quartile 1, 95% CI 0.01 to 0.50; p = 0.009). Conclusion: Autophagic flux is elevated in PBMCs from ASVD patients, independent of age and sex. Attenuated flux in CLTI with concurrent infection may indicate autophagic exhaustion in advanced disease. The association between higher flux and lower MACE in CLTI suggests prognostic utility, warranting evaluation in larger prospective studies.

pathology↗

Quantitative Model of the Ocular Immune Response during Seasonal Allergic Conjunctivitis

Allergic conjunctivitis is an inflammation of the conjunctiva caused by allergen; it is common disorder affecting up to 40% of the population. In this work, we study seasonal allergic conjunctivitis (SAC), also called "hay fever eyes", which is caused by exposure to airborne pollens. We develop a mathematical model quantifying the ocular immune system response to the allergens. First, we present a simplified qualitative description of the immunopathogenesis of SAC. Then, we express each chosen immunopathological mechanism mathematically to construct a system of thirty-one ordinary differential equations. We compare summary statistics of the predicted observable immune signals to experimental measurements and find our model captures key qualitative features of SAC progression. We then compare our predicted time series of histamine concentration to symptom scores and find a strong correlation suggesting the model predicts relevant clinically trends. Next, we calibrate the model through multi-step process. We find the most influential parameters are the production and depletion rates of IL-4, and the production rates of IL-5 and IL-8. These cytokines are targeted in treatments for asthma, atopic dermatitis, and severe eosinophilic associated disorder and suggest potential therapeutic targets for SAC. Our calibrated model mimics most of the summary statistics of the experimentally observable immune signals with discrepancies for IL-5 and IL-13 indicating that additional immunopathological mechanisms could be important.

pathology↗

Dysregulated Platelet GPIb alpha - VWF Signalling in Abdominal Aortic Aneurysm formation and Progression

Background: Platelets are critical drivers of thrombo-inflammatory responses in different cardiovascular diseases. Abdominal aortic aneurysm (AAA) is a progressive, life-threatening vascular disorder mainly characterised by chronic inflammation, extracellular matrix degradation, and the formation of a platelet-rich intraluminal thrombus (ILT). Experimental and clinical evidence identified platelets as main players in AAA pathology as evidenced by elevated platelet activation and procoagulant activity that critically contribute to AAA progression. Methods: The present study investigated the contribution of glycoprotein (GP)Ib alpha, the von Willebrand factor (VWF)-binding subunit of the platelet GPIb-IX-V complex, to AAA initiation and progression in experimental AAA using the ePPE mouse model and in patients. Results: Genetic ablation of platelet GPIb alpha significantly attenuated early aneurysm expansion in experimental AAA, indicating a critical role for GPIb alpha during the initial stages of aneurysm development. This initial effect was compensated at later time points showing no differences in aneurysm progression between groups. Notably, genetic deletion of GPIb alpha induced a constitutively hyperactive platelet phenotype already in naive mice that was further amplified during experimental AAA. This elevated platelet hyperactivity was mainly due to increased GPVI activation of platelets 28 days post-surgery. To assess the clinical relevance, spatial profiles of human ILT specimens from patients with AAA were analysed. In the ILT, we detected a highly compartmentalised distribution of GPIb alpha and VWF with pronounced enrichment within the luminal layer. In parallel, circulating VWF activity as well as platelet surface expression of GPIb alpha were significantly increased in patients with AAA. Conclusion: Collectively, these findings identify a dysregulated GPIb alpha-VWF axis in human AAA pathology, mainly characterised by enhanced platelet GPIb alpha surface expression and increased activity of circulating VWF.

pathology↗