Academic Journal
Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts
| Τίτλος: | Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts |
|---|---|
| Συγγραφείς: | Li Y, Saba L, Scheinman RI, Banda NK, Holers M, Monte A, Dylla L, Moghimi SM, Simberg D |
| Πηγή: | ACS Nano, 22 October 2024 |
| Στοιχεία εκδότη: | American Chemical Society |
| Έτος έκδοσης: | 2024 |
| Συλλογή: | Newcastle University Library ePrints Service |
| Περιγραφή: | © 2024 American Chemical Society.Systemic administration of nanomedicines results in the activation of the complement cascade, promoting phagocytic uptake and triggering proinflammatory responses. Identifying the biomarkers that can predict the “risk” of abnormally high complement responders can improve the safety and efficacy of nanomedicines. Polyethylene glycol (PEG) and dextran are two types of clinically approved polymer coatings that trigger complement activation. We performed a multifaceted analysis of the factors affecting the complement activation by PEGylated liposomal doxorubicin (PLD) and dextran-coated superparamagnetic iron oxide nanoworms (SPIO NWs) in plasma from patients with different inflammatory disease conditions and healthy donors. The complement activation (measured as deposition of the complement protein C3) varied greatly, with 29-fold and 26-fold differences for PLD and SPIO NWs, respectively. Chronic inflammation, acute infection, use of steroids, and sex had minor effects on the variable complement activation, whereas age inversely correlated with the complement activation. C-reactive protein level was not predictive of high (top 20th percentile) complement responses. Plasma concentrations of the main complement factors, as well as total IgG and IgM, showed no correlation with the activation by either nanoparticle. On the other hand, plasma concentrations of anti-PEG IgG and IgM showed a strong positive correlation with the activation by PLD. Particularly, titers of anti-PEG IgM showed the best predictive value for the “risk” of high complement activation by PLD. Titers of antidextran IgG and IgM showed a lower correlation with the activation by SPIO NWs and poor predictive value of the top 20% complement responses. Nanoparticle-bound immunoglobulins showed the best correlation with complement activation and a strong predictive value, supporting the critical role of immunoglobulins in inciting complement. The opsonization of PLD with C3 in plasma with high anti-PEG antibodies was ... |
| Τύπος εγγράφου: | article in journal/newspaper |
| Γλώσσα: | unknown |
| Relation: | https://eprints.ncl.ac.uk/302250 |
| Διαθεσιμότητα: | https://eprints.ncl.ac.uk/302250 |
| Αριθμός Καταχώρησης: | edsbas.46DCD560 |
| Βάση Δεδομένων: | BASE |
| FullText | Text: Availability: 0 CustomLinks: – Url: https://eprints.ncl.ac.uk/302250# Name: EDS - BASE (ns324271) Category: fullText Text: View record from BASE |
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| Header | DbId: edsbas DbLabel: BASE An: edsbas.46DCD560 RelevancyScore: 875 AccessLevel: 3 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 874.983581542969 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Li+Y%22">Li Y</searchLink><br /><searchLink fieldCode="AR" term="%22Saba+L%22">Saba L</searchLink><br /><searchLink fieldCode="AR" term="%22Scheinman+RI%22">Scheinman RI</searchLink><br /><searchLink fieldCode="AR" term="%22Banda+NK%22">Banda NK</searchLink><br /><searchLink fieldCode="AR" term="%22Holers+M%22">Holers M</searchLink><br /><searchLink fieldCode="AR" term="%22Monte+A%22">Monte A</searchLink><br /><searchLink fieldCode="AR" term="%22Dylla+L%22">Dylla L</searchLink><br /><searchLink fieldCode="AR" term="%22Moghimi+SM%22">Moghimi SM</searchLink><br /><searchLink fieldCode="AR" term="%22Simberg+D%22">Simberg D</searchLink> – Name: TitleSource Label: Source Group: Src Data: ACS Nano, 22 October 2024 – Name: Publisher Label: Publisher Information Group: PubInfo Data: American Chemical Society – Name: DatePubCY Label: Publication Year Group: Date Data: 2024 – Name: Subset Label: Collection Group: HoldingsInfo Data: Newcastle University Library ePrints Service – Name: Abstract Label: Description Group: Ab Data: © 2024 American Chemical Society.Systemic administration of nanomedicines results in the activation of the complement cascade, promoting phagocytic uptake and triggering proinflammatory responses. Identifying the biomarkers that can predict the “risk” of abnormally high complement responders can improve the safety and efficacy of nanomedicines. Polyethylene glycol (PEG) and dextran are two types of clinically approved polymer coatings that trigger complement activation. We performed a multifaceted analysis of the factors affecting the complement activation by PEGylated liposomal doxorubicin (PLD) and dextran-coated superparamagnetic iron oxide nanoworms (SPIO NWs) in plasma from patients with different inflammatory disease conditions and healthy donors. The complement activation (measured as deposition of the complement protein C3) varied greatly, with 29-fold and 26-fold differences for PLD and SPIO NWs, respectively. Chronic inflammation, acute infection, use of steroids, and sex had minor effects on the variable complement activation, whereas age inversely correlated with the complement activation. C-reactive protein level was not predictive of high (top 20th percentile) complement responses. Plasma concentrations of the main complement factors, as well as total IgG and IgM, showed no correlation with the activation by either nanoparticle. On the other hand, plasma concentrations of anti-PEG IgG and IgM showed a strong positive correlation with the activation by PLD. Particularly, titers of anti-PEG IgM showed the best predictive value for the “risk” of high complement activation by PLD. Titers of antidextran IgG and IgM showed a lower correlation with the activation by SPIO NWs and poor predictive value of the top 20% complement responses. Nanoparticle-bound immunoglobulins showed the best correlation with complement activation and a strong predictive value, supporting the critical role of immunoglobulins in inciting complement. The opsonization of PLD with C3 in plasma with high anti-PEG antibodies was ... – Name: TypeDocument Label: Document Type Group: TypDoc Data: article in journal/newspaper – Name: Language Label: Language Group: Lang Data: unknown – Name: NoteTitleSource Label: Relation Group: SrcInfo Data: https://eprints.ncl.ac.uk/302250 – Name: URL Label: Availability Group: URL Data: https://eprints.ncl.ac.uk/302250 – Name: AN Label: Accession Number Group: ID Data: edsbas.46DCD560 |
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| RecordInfo | BibRecord: BibEntity: Languages: – Text: unknown Titles: – TitleFull: Nanoparticle-Binding Immunoglobulins Predict Variable Complement Responses in Healthy and Diseased Cohorts Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Li Y – PersonEntity: Name: NameFull: Saba L – PersonEntity: Name: NameFull: Scheinman RI – PersonEntity: Name: NameFull: Banda NK – PersonEntity: Name: NameFull: Holers M – PersonEntity: Name: NameFull: Monte A – PersonEntity: Name: NameFull: Dylla L – PersonEntity: Name: NameFull: Moghimi SM – PersonEntity: Name: NameFull: Simberg D IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 01 Type: published Y: 2024 Identifiers: – Type: issn-locals Value: edsbas Titles: – TitleFull: ACS Nano, 22 October 2024 Type: main |
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