Platelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy.
Platelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy.
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DOI：
10.34133/2022/9845459
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Chen L;Zhou Z;Hu C;Maitz MF;Yang L;Luo R;Wang Y
动脉粥样硬化是全世界心血管疾病（CVD）的主要原因，其主要特征是病变血管细胞和凋亡细胞碎片的病理性积累。动脉粥样硬化形成与 CD47 的上调有关，CD47 是一种关键的抗吞噬细胞分子，已知可使恶性细胞对程序性细胞去除或“胞吞作用”产生抵抗力。在这里，我们开发了血小板膜包被的介孔硅纳米颗粒（PMSN）作为药物递送系统，通过递送抗 CD47 抗体来靶向动脉粥样硬化斑块。简而言之，细胞膜涂层通过逃避免疫识别来延长颗粒的循环，并提供对斑块和动脉粥样硬化部位的亲和力。然后，抗 CD47 抗体使患病血管组织的清除正常化，并通过阻断 CD47 进一步改善动脉粥样硬化。在 ApoE−/− 小鼠建立的动脉粥样硬化模型中，包裹抗 CD47 抗体的 PMSN 显着促进斑块中坏死细胞的胞吞作用。清除坏死细胞大大减少了动脉粥样硬化斑块面积并稳定了斑块，降低了斑块破裂和晚期血栓形成的风险。总体而言，本研究证明了 PMSN 封装抗 CD47 抗体用于动脉粥样硬化治疗的治疗优势，作为有效治疗动脉粥样硬化的新型靶向药物递送平台具有广阔的前景。
Atherosclerosis, the principle cause of cardiovascular disease (CVD) worldwide, is mainly characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris. Atherogenesis is associated with the upregulation of CD47, a key antiphagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or “efferocytosis.” Here, we have developed platelet membrane-coated mesoporous silicon nanoparticles (PMSN) as a drug delivery system to target atherosclerotic plaques with the delivery of an anti-CD47 antibody. Briefly, the cell membrane coat prolonged the circulation of the particles by evading the immune recognition and provided an affinity to plaques and atherosclerotic sites. The anti-CD47 antibody then normalized the clearance of diseased vascular tissue and further ameliorated atherosclerosis by blocking CD47. In an atherosclerosis model established in ApoE−/− mice, PMSN encapsulating anti-CD47 antibody delivery significantly promoted the efferocytosis of necrotic cells in plaques. Clearing the necrotic cells greatly reduced the atherosclerotic plaque area and stabilized the plaques reducing the risk of plaque rupture and advanced thrombosis. Overall, this study demonstrated the therapeutic advantages of PMSN encapsulating anti-CD47 antibodies for atherosclerosis therapy, which holds considerable promise as a new targeted drug delivery platform for efficient therapy of atherosclerosis.
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影响因子：
64.8
作者：
Kojima Y;Volkmer JP;McKenna K;Civelek M;Lusis AJ;Miller CL;Direnzo D;Nanda V;Ye J;Connolly AJ;Schadt EE;Quertermous T;Betancur P;Maegdefessel L;Matic LP;Hedin U;Weissman IL;Leeper NJ
通讯作者：
Leeper NJ
影响因子：
17.1
作者：
Kamaly, Nazila;Fredman, Gabrielle;Fojas, Jhalique Jane R.;Subramanian, Manikandan;Choi, Won Ii;Zepeda, Katherine;Vilos, Cristian;Yu, Mikyung;Gadde, Suresh;Wu, Jun;Milton, Jaclyn;Leitao, Renata Carvalho;Fernandes, Livia Rosa;Hasan, Moaraj;Gao, Huayi;Vance Nguyen;Harris, Jordan;Tabas, Ira;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.
一种吸收孔形成毒素的仿生纳米质体。
影响因子：
38.3
作者：
通讯作者：
--
DOI：
10.1073/pnas.1106634108
发表时间：
2011-07-05
影响因子：
11.1
作者：
Hu, Che-Ming J.;Zhang, Li;Zhang, Liangfang
通讯作者：
Zhang, Liangfang
影响因子：
17.1
作者：
Fredman G;Kamaly N;Spolitu S;Milton J;Ghorpade D;Chiasson R;Kuriakose G;Perretti M;Farokzhad O;Tabas I
通讯作者：
Tabas I