TY - JOUR

T1 - Nanometer- and angstrom-scale characteristics that modulate complement responses to nanoparticles

AU - Moghimi, S. Moein

AU - Haroon, Hajira B.

AU - Yaghmur, Anan

AU - Simberg, Dmitri

AU - Trohopoulos, Panagiotis N.

N1 - Funding Information: S.M.M. acknowledges support by the European Union's Horizon 2020 programme funded under H2020-EU.1.3. – Excellent Science – Marie Sklodowska-Curie Actions, grant agreement ID. 956544 (DIRNANO: Directing the immune response through designed nanomaterials). H.B.H. is an Early Stage Researcher supported by the DIRNANO programme. A.Y. & S.M.M. acknowledge support by the Danish Council for Independent Research – Technology and Production Sciences; reference DFF-7017-00065. P.N.T. & S.M.M. acknowledge support by the European Union's Seventh Framework Programme (FP7-NMP-2012-Large-6) under the grant agreement no. 310337 (CosmoPHOS-nano Large-Scale Project). D.S. acknowledges support by the National Institute of Health grant R01AI154959. Funding Information: S.M.M. acknowledges support by the European Union's Horizon 2020 programme funded under H2020-EU.1.3 . – Excellent Science – Marie Sklodowska-Curie Actions , grant agreement ID. 956544 (DIRNANO: Directing the immune response through designed nanomaterials). H.B.H. is an Early Stage Researcher supported by the DIRNANO programme. A.Y. & S.M.M. acknowledge support by the Danish Council for Independent Research – Technology and Production Sciences ; reference DFF-7017-00065 . P.N.T. & S.M.M. acknowledge support by the European Union's Seventh Framework Programme (FP7-NMP-2012-Large-6) under the grant agreement no. 310337 (CosmoPHOS-nano Large-Scale Project). D.S. acknowledges support by the National Institute of Health grant R01AI154959 . Publisher Copyright: © 2022 The Authors

PY - 2022

Y1 - 2022

N2 - The contribution of the complement system to non-specific host defence and maintenance of homeostasis is well appreciated. Many particulate systems trigger complement activation but the underlying mechanisms are still poorly understood. Activation of the complement cascade could lead to particle opsonisation by the cleavage products of the third complement protein and might promote inflammatory reactions. Antibody binding in a controlled manner and/or sensing of particles by the complement pattern-recognition molecules such as C1q and mannose-binding lectin can trigger complement activation. Particle curvature and spacing arrangement/periodicity of surface functional groups/ligands are two important parameters that modulate complement responses through multivalent engagement with and conformational regulation of surface-bound antibodies and complement pattern-recognition molecules. Thus, a better fundamental understanding of nanometer- and angstrom-scale parameters that modulate particle interaction with antibodies and complement proteins could portend new possibilities for engineering of particulate drug carriers and biomedical platforms with tuneable complement responses and is discussed here.

AB - The contribution of the complement system to non-specific host defence and maintenance of homeostasis is well appreciated. Many particulate systems trigger complement activation but the underlying mechanisms are still poorly understood. Activation of the complement cascade could lead to particle opsonisation by the cleavage products of the third complement protein and might promote inflammatory reactions. Antibody binding in a controlled manner and/or sensing of particles by the complement pattern-recognition molecules such as C1q and mannose-binding lectin can trigger complement activation. Particle curvature and spacing arrangement/periodicity of surface functional groups/ligands are two important parameters that modulate complement responses through multivalent engagement with and conformational regulation of surface-bound antibodies and complement pattern-recognition molecules. Thus, a better fundamental understanding of nanometer- and angstrom-scale parameters that modulate particle interaction with antibodies and complement proteins could portend new possibilities for engineering of particulate drug carriers and biomedical platforms with tuneable complement responses and is discussed here.

KW - Antibodies

KW - C1q

KW - Complement system

KW - Dendrimers

KW - Factor H

KW - Mannose-binding lectin

KW - Nanoparticles

U2 - 10.1016/j.jconrel.2022.09.039

DO - 10.1016/j.jconrel.2022.09.039

M3 - Journal article

C2 - 36152807

AN - SCOPUS:85138484219

VL - 351

SP - 432

EP - 443

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -