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Modular design of Bi-specific nanoplatform engaged in malignant lymphoma immunotherapy.
Nanoscale ( IF 5.8 ) Pub Date : 2020-08-18 , DOI: 10.1039/d0nr04450d
Chen Bai 1 , Pengcheng Hu , Wei Zhang , Lina Song , Di Liu , Yi Chen , Ming Ma , Ning Gu , Yu Zhang
Affiliation  

Nanocarrier systems play an important role in cancer immunotherapy. In this article, biotinylated CD20 and CD3 antibodies were conjugated onto the surface of streptavidin modified ultra-small Fe3O4 nanoparticles via specific binding between streptavidin and biotin to construct a bi-specific nanoplatform (BSNP). The synthesized BSNP with 30 nm hydrodynamic size provides a better magnetic resonance imaging ability than the clinical Gd-chelated contrast agents (r1 value is 5.27 mM−1 s−1 and 4.52 mM−1 s−1 for BSNP and Magnevist, respectively). This nanoplatform can target CD20-positive Raji cells and enhance the T cell mediated cell killing effect in vitro. Further, it can also inhibit tumor growth and prolong the survival time of non-Hodgkin's lymphoma (NHL) xenograft model in vivo. The probable mechanism is that while BSNP can directly induce the apoptosis of Raji cell via aggregation of CD20, T cells are recruited around tumor cells by the BSNP leading to T cell-mediated tumor cell lysis. In addition, the enhanced dual-modal MRI-fluorescence images can be acquired. In summary, the modular designed BSNP provides an efficient immune-related cancer theranostic strategy, which is of great potential as a simple and universal nanoplatform by combining different antibodies to enhance the cancer theranostic efficacy.

中文翻译:

参与恶性淋巴瘤免疫治疗的Bi特异性纳米平台的模块化设计。

纳米载体系统在癌症免疫治疗中起重要作用。在本文中,通过链霉亲和素和生物素之间的特异性结合,将生物素化的CD20和CD3抗体偶联到链霉亲和素修饰的超小Fe 3 O 4纳米颗粒的表面上,以构建双特异性纳米平台(BSNP)。合成的BSNP具有30 nm的流体动力学尺寸,比临床的Gd螯合造影剂具有更好的磁共振成像能力(r 1值为5.27 mM -1 s -1和4.52 mM -1 s -1分别用于BSNP和Magnevist)。这种纳米平台可以靶向CD20阳性的Raji细胞,并在体外增强T细胞介导的细胞杀伤作用。此外,还可以抑制肿瘤生长,延长非何杰金氏淋巴瘤(NHL)异种移植模型中的存活时间在体内。可能的机理是,虽然可以BSNP直接诱导的Raji细胞凋亡经由CD20的聚集,通过BSNP在肿瘤细胞周围募集T细胞,导致T细胞介导的肿瘤细胞裂解。另外,可以获取增强的双峰MRI荧光图像。总之,模块化设计的BSNP提供了有效的免疫相关的癌症治疗策略,通过结合不同的抗体来增强癌症治疗功效,作为简单通用的纳米平台具有巨大的潜力。
更新日期:2020-09-18
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