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.
Резюме
Complement is one of the critical branches of innate immunity that determines the recognition of engineered nanoparticles by immune cells.
Почему это важно для гирудотерапии
This study investigated how complement C3 opsonization affects the targeting selectivity of antibody-conjugated iron oxide nanoparticles (nanoworms) in whole human blood, using lepirudin-anticoagulated blood as the assay matrix. Lepirudin served as the anticoagulant for blood collection, not as an investigational agent. The study showed that complement inhibitors (compstatin, soluble CD35, soluble CD55) blocked up to 99% of nanoparticle uptake by leukocytes, improving tumor-cell targeting selectivity. For ASH's domain, the relevance is minimal and incidental: lepirudin is used purely as a blood-collection anticoagulant in the assay. No aspect of hirudotherapy or the leech secretome is investigated, and the abstract does not describe lepirudin's biochemical origin or rationale for use.
Цитирование
Complement Inhibitors Block Complement C3 Opsonization and Improve Targeting Selectivity of Nanoparticles in Blood
Gaikwad H et al. · Bioconjugate chemistry, 2020
Связанный клинический контекст
Узнайте, как это исследование связано с клинической практикой
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