Nanomedicine is considered a promising alternative to improve cancer diagnosis and treatment. Particularly, the use of nanoparticles (NPs) has enabled the encapsulation of highly toxic anticancer drugs, facilitated ultimate targeting, and allowed tailoring of drug delivery. However, when in biological fluids, these NPs are coated by proteins which hide the targeting moieties and suppress the engineered biological outcome. Herein, how the Ki‐1 monoclonal antibody (mAb) can preserve its targetability through grafting on the surface of zwitterionic‐functionalized nanoparticles, is unveiled. Zwitterions, known for their stealth ability, are used to minimize unspecific NPs protein adsorption and consequently maintain mAb functionality. In this work, Ki‐1 mAb is used as it recognizes TNFRSF8 (CD30⁺) transmembrane protein overexpressed on CD30⁺ lymphoma cells such as L540 cells. While nonfunctionalized NPs show negligible toxic effects toward L540 cells, the Ki‐1‐functionalized structure demonstrates cytotoxicity, since they undergo cellular uptake, suggesting a receptor‐mediated internalization. This dual‐functionalization strategy provides a promising multifunctional nanoplatform toward future personalized medicine applications, minimizing unspecific protein adsorption on NPs and ensuring selective cancer cell targeting.

中文翻译：

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通过两性离子功能化纳米粒子上嫁接的单克隆抗体对淋巴瘤细胞的选择性靶向。

纳米医学被认为是改善癌症诊断和治疗的有希望的替代方法。特别地，纳米颗粒（NPs）的使用使得能够封装高毒性的抗癌药物，促进最终靶向，并允许定制药物递送。然而，当处于生物流体中时，这些NP被蛋白质包被，该蛋白质掩盖了靶向部分并抑制了工程化的生物学结果。本文揭示了Ki-1单克隆抗体（mAb）如何通过在两性离子官能化的纳米颗粒表面上进行嫁接来保持其可靶向性。以其隐身能力闻名的两性离子可用于最大程度地减少非特异性NPs蛋白质的吸附，从而保持mAb的功能。在这项工作中，使用Ki-1 mAb来识别TNFRSF8（CD30 ⁺）跨膜蛋白在CD30 ⁺淋巴瘤细胞（如L540细胞）上过表达。尽管未官能化的NPs对L540细胞的毒性作用可忽略不计，但Ki-1官能化的结构却表现出细胞毒性，因为它们会被细胞吸收，表明受体介导的内在化。这种双重功能化策略为未来的个性化医学应用提供了有希望的多功能纳米平台，可最大程度地减少非特异性蛋白质在NP上的吸附并确保选择性靶向癌细胞。