Surface Geometry of Cargo-less Gold Nanoparticles Is a Driving Force for Selective Targeting of Activated Neutrophils to Reduce Thrombosis in Antiphospholipid Syndrome.
Surface Geometry of Cargo-less Gold Nanoparticles Is a Driving Force for Selective Targeting of Activated Neutrophils to Reduce Thrombosis in Antiphospholipid Syndrome.
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DOI：
10.1021/acs.nanolett.3c02075
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发表时间：
2023-11-08
期刊：
影响因子：
10.8
通讯作者：
Maiseyeu A
中科院分区：
文献类型：
--
作者：
Di L;Thomas A;Switala L;Kalikasingh K;Lapping S;Nayak L;Maiseyeu A
抗磷脂综合征（APS）是一种自身免疫性疾病，以动脉、静脉和微血管血栓形成为特征，其中活化的中性粒细胞起决定性作用。然而，鉴于中性粒细胞在循环中的寿命较短和自发激活，靶向它们是具有挑战性的。筛选一个小的金纳米颗粒（AuNPs）库导致发现了一种能够靶向活化的中性粒细胞附着的配方，并证明了星形的抗psgl -1抗体包被的AuNPs （aPSGL-1-AuNPs）比其他形状的AuNPs更有效。我们的研究结果进一步揭示了人类患者源性抗磷脂igg诱导的APS小鼠模型中活化中性粒细胞的令人兴奋和安全的靶向模式。我们的研究表明，靶向性取决于活化的中性粒细胞表面上高度分离的PSGL-1的特定地形特征，因此可以设计和实施高亲和力形状驱动的纳米药物。因此，星形aPSGL-1-AuNPs作为一种有前景的纳米免疫疗法，用于治疗APS中与中性粒细胞粘附相关的免疫血栓形成。
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arterial, venous, and microvascular thrombosis where activated neutrophils play a determinant role. However, neutrophils are challenging to target given their short lifespan in circulation and spontaneous activation. Screening of a small library of gold nanoparticles (AuNPs) led to the discovery of a formulation capable of targeting activated neutrophil attachment and has demonstrated that star-shaped, anti-PSGL-1-antibody-coated AuNPs (aPSGL-1-AuNPs) were more efficacious compared with other shapes of AuNPs. Our findings further revealed an exciting and safe targeting mode toward activated neutrophils in the APS mouse model induced by human-patient-derived antiphospholipid IgGs. Our studies demonstrate that targeting is dependent on the specific topographical features of the highly segregated PSGL-1 on the activated neutrophil surface for which a high affinity shape-driven nanomedicine can be designed and implemented. As such, star-shaped aPSGL-1-AuNPs serve as a promising nanoimmunotherapy for immunothrombosis associated with neutrophil adhesion in APS.
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影响因子：
--
作者：
Kappelmayer J;Nagy B Jr
通讯作者：
Nagy B Jr
影响因子：
17.1
作者：
Lin, Zhoumeng;Aryal, Santosh;Cheng, Yi-Hsien;Gesquiere, Andre J.
通讯作者：
Gesquiere, Andre J.
影响因子：
20.3
作者：
Abbal, Claire;Lambelet, Martine;Spertini, Olivier
通讯作者：
Spertini, Olivier
DOI：
10.1083/jcb.128.4.661
发表时间：
1995-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Moore KL;Patel KD;Bruehl RE;Li F;Johnson DA;Lichenstein HS;Cummings RD;Bainton DF;McEver RP
通讯作者：
McEver RP
影响因子：
--
作者：
Luo YH;Chang LW;Lin P
通讯作者：
Lin P