ArticleInternational journal of nanomedicine2018
Involvement of complement activation in the pulmonary vasoactivity of polystyrene nanoparticles in pigs: unique surface properties underlying alternative pathway activation and instant opsonization.
Article in International journal of nanomedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Meta-Analysis and Machine Learning Prediction of Protein Corona Composition across Nanoparticle Systems in Biological Media.ACS nano · 2025Pooled it
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- Evaluation of the Acute Anaphylactoid Reactogenicity of Nanoparticle-Containing Medicines and Vaccines Using the Porcine CARPA Model.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Zymosan Particle-Induced Hemodynamic, Cytokine and Blood Cell Changes in Pigs: An Innate Immune Stimulation Model with Relevance to Cytokine Storm Syndrome and Severe COVID-19.International journal of molecular sciences · 2023Article
- Comparative in vitro and in vivo Evaluation of Different Iron Oxide-Based Contrast Agents to Promote Clinical Translation in Compliance with Patient Safety.International journal of nanomedicine · 2023Article
- Article
- Lessons learned from immunological characterization of nanomaterials at the Nanotechnology Characterization Laboratory.Frontiers in immunology · 2022Review
- Role of Surface Charge of Nanoscale Ultrasound Contrast Agents in Complement Activation and Phagocytosis.International journal of nanomedicine · 2022Article
- Screening and prioritization of nano- and microplastic particle toxicity studies for evaluating human health risks - development and application of a toxicity study assessment tool.Microplastics and nanoplastics · 2022Article
- A porcine model of hemodialyzer reactions: roles of complement activation and rinsing back of extracorporeal blood.Renal failure · 2021Article
- Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Roadmap on nanomedicine.Nanotechnology · 2021Article
- Development of a Sensitive Assay to Screen NanoparticlesACS biomaterials science & engineering · 2020Article
- Human Clinical Relevance of the Porcine Model of Pseudoallergic Infusion Reactions.Biomedicines · 2020Review
- Nanoparticle-Induced Complement Activation: Implications for Cancer Nanomedicine.Frontiers in immunology · 2020Review
- The Interplay Between Blood Proteins, Complement, and Macrophages on Nanomedicine Performance and Responses.The Journal of pharmacology and experimental therapeutics · 2019Review
- Acute physiological changes caused by complement activators and amphotericin B-containing liposomes in mice.International journal of nanomedicine · 2019Article
- Roadmap and strategy for overcoming infusion reactions to nanomedicines.Nature nanotechnology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIt has been proposed that many hypersensitivity reactions to nanopharmaceuticals represent complement (C)-activation-related pseudoallergy (CARPA), and that pigs provide a sensitive animal model to study the phenomenon. However, a recent study suggested that pulmonary hypertension, the pivotal symptom of porcine CARPA, is not mediated by C in cases of polystyrene nanoparticle (PS-NP)-induced reactions. GOALS: To characterize PS-NPs and reexamine the contribution of CARPA to their pulmonary reactivity in pigs. STUDY
designC activation by 200, 500, and 750 nm (diameter) PS-NPs and their opsonization were measured in human and pig sera, respectively, and correlated with hemodynamic effects of the same NPs in pigs in vivo.
methodsPhysicochemical characterization of PS-NPs included size, ζ-potential, cryo-transmission electron microscopy, and hydrophobicity analyses. C activation in human serum was measured by ELISA and opsonization of PS-NPs in pig serum by Western blot and flow cytometry. Pulmonary vasoactivity of PS-NPs was quantified in the porcine CARPA model.
resultsPS-NPs are monodisperse, highly hydrophobic spheres with strong negative surface charge. In human serum, they caused size-dependent, significant rises in C3a, Bb, and sC5b-9, but not C4d. Exposure to pig serum led within minutes to deposition of C5b-9 and opsonic iC3b on the NPs, and opsonic iC3b fragments (C3dg, C3d) also appeared in serum. PS-NPs caused major hemodynamic changes in pigs, primarily pulmonary hypertension, on the same time scale (minutes) as iC3b fragmentation and opsonization proceeded. There was significant correlation between C activation by different PS-NPs in human serum and pulmonary hypertension in pigs.
conclusionPS-NPs have extreme surface properties with no relevance to clinically used nanomedicines. They can activate C via the alternative pathway, entailing instantaneous opsonization of NPs in pig serum. Therefore, rather than being solely C-independent reactivity, the mechanism of PS-NP-induced hypersensitivity in pigs may involve C activation. These data are consistent with the "double-hit" concept of nanoparticle-induced hypersensitivity reactions involving both CARPA and C-independent pseudoallergy.
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