Your browser doesn't support javascript.
loading
Complement Inhibitors Block Complement C3 Opsonization and Improve Targeting Selectivity of Nanoparticles in Blood.
Gaikwad, Hanmant; Li, Yue; Gifford, Geoffrey; Groman, Ernest; Banda, Nirmal K; Saba, Laura; Scheinman, Robert; Wang, Guankui; Simberg, Dmitri.
Afiliação
  • Banda NK; Division of Rheumatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States.
Bioconjug Chem ; 31(7): 1844-1856, 2020 07 15.
Article em En | MEDLINE | ID: mdl-32598839
Complement is one of the critical branches of innate immunity that determines the recognition of engineered nanoparticles by immune cells. Antibody-targeted iron oxide nanoparticles are a popular platform for magnetic separations, in vitro diagnostics, and molecular imaging. We used 60 nm cross-linked iron oxide nanoworms (CLIO NWs) modified with antibodies against Her2/neu and EpCAM, which are common markers of blood-borne cancer cells, to understand the role of complement in the selectivity of targeting of tumor cells in whole blood. CLIO NWs showed highly efficient targeting and magnetic isolation of tumor cells spiked in lepirudin-anticoagulated blood, but specificity was low due to high uptake by neutrophils, monocytes, and lymphocytes. Complement C3 opsonization in plasma was predominantly via the alternative pathway regardless of the presence of antibody, PEG, or fluorescent tag, but was higher for antibody-conjugated CLIO NWs. Addition of various soluble inhibitors of complement convertase (compstatin, soluble CD35, and soluble CD55) to whole human blood blocked up to 99% of the uptake of targeted CLIO NWs by leukocytes, which resulted in a more selective magnetic isolation of tumor cells. Using well-characterized nanomaterials, we demonstrate here that complement therapeutics can be used to improve targeting selectivity.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Complemento C3 / Linfócitos / Monócitos / Inativadores do Complemento / Nanopartículas / Neutrófilos Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Complemento C3 / Linfócitos / Monócitos / Inativadores do Complemento / Nanopartículas / Neutrófilos Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article