Complement Inhibitors Block Complement C3 Opsonization and Improve Targeting Selectivity of Nanoparticles in Blood
Research article published in Bioconjugate chemistry (2020)
Abstract
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Complement is one of the critical branches of innate immunity that determines the recognition of engineered nanoparticles by immune cells.
Por qué esto importa para la hirudoterapia
Este estudio investigó cómo la opsonización por complemento C3 afecta la selectividad de targeting de nanopartículas de óxido de hierro conjugadas con anticuerpos (nanoworms) en sangre humana completa, utilizando sangre anticoagulada con lepirudina como matriz del ensayo. La lepirudina sirvió como anticoagulante para la recolección de sangre, no como agente en investigación. El estudio demostró que los inhibidores del complemento (compstatina, CD35 soluble, CD55 soluble) bloquearon hasta el 99% de la captación de nanopartículas por los leucocitos, mejorando la selectividad de targeting hacia las células tumorales. Para el ámbito de ASH, la relevancia es mínima e incidental: la lepirudina se utiliza puramente como anticoagulante para la recolección de sangre en el ensayo. No se investiga ningún aspecto de la hirudoterapia o del secretoma de la sanguijuela, y el resumen no describe el origen bioquímico ni la justificación de uso de la lepirudina.
Citación
Complement Inhibitors Block Complement C3 Opsonization and Improve Targeting Selectivity of Nanoparticles in Blood
Gaikwad H et al. · Bioconjugate chemistry, 2020
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026