Complement Inhibitors Block Complement C3 Opsonization and Improve Targeting Selectivity of Nanoparticles in Blood.
Complement Inhibitors Block Complement C3 Opsonization and Improve Targeting Selectivity of Nanoparticles in Blood.
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DOI：
10.1021/acs.bioconjchem.0c00342
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发表时间：
2020-07-15
影响因子：
4.7
通讯作者：
Simberg D
中科院分区：
文献类型：
--
作者：
Gaikwad H;Li Y;Gifford G;Groman E;Banda NK;Saba L;Scheinman R;Wang G;Simberg D
补体是先天免疫的关键分支之一，决定了免疫细胞对工程纳米颗粒的识别。抗体靶向的氧化铁纳米颗粒是用于磁分离、体外诊断和分子成像的流行平台。我们使用了60 nm交联氧化铁纳米颗粒（克利奥NW），其用针对Her 2/neu和EpCAM的抗体修饰，这是血液传播的癌细胞的常见标志物，以了解补体在全血中靶向肿瘤细胞的选择性中的作用。克利奥NW显示出对加标在来匹鲁定抗凝血液中的肿瘤细胞的高效靶向和磁性分离，但由于嗜中性粒细胞、单核细胞和淋巴细胞的高摄取，特异性较低。无论是否存在抗体、PEG或荧光标签，血浆中的补体C3调理作用主要通过旁路途径，但抗体缀合的克利奥NW更高。向人全血中添加补体转化酶的各种可溶性抑制剂（坎普他汀、可溶性⑶ 35和可溶性⑶ 55）阻断了高达99%的白细胞对靶向克利奥NW的摄取，这导致肿瘤细胞的更具选择性的磁性分离。使用良好表征的纳米材料，我们在这里证明，补体治疗可用于提高靶向选择性。
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.
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影响因子：
16.6
作者：
Cheng F;Desai RJ;Handy DE;Wang R;Schneeweiss S;Barabási AL;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
3.7
作者：
Borchard, G;Kreuter, J
通讯作者：
Kreuter, J
DOI：
10.1073/pnas.0404036101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Krivacic, RT;Ladanyi, A;Bruce, RH
通讯作者：
Bruce, RH
影响因子：
15.3
作者：
FRIES, LF;GAITHER, TA;FRANK, MM
通讯作者：
FRANK, MM
影响因子：
10.8
作者：
Gifford, Geoffrey;Vu, Vivian P.;Simberg, Dmitri
通讯作者：
Simberg, Dmitri