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用于增强循环肿瘤细胞分离的人工细胞膜伪装免疫磁性纳米颗粒

Artificial cell membrane camouflaged immunomagnetic nanoparticles for enhanced circulating tumor cell isolation.

作者信息

Zhou Xiaoxi, Zhang Yujia, Kang Ke, Zhu Nanhang, Cheng Jia, Yi Qiangying, Wu Yao

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, P. R. China.

出版信息

J Mater Chem B. 2022 Apr 20;10(16):3119-3125. doi: 10.1039/d1tb02676c.

DOI:10.1039/d1tb02676c
PMID:35348557
Abstract

Precise and specific circulating tumor cell (CTC) isolation is heavily interfered with by blood cells and proteins. Although satisfactory results have been achieved by some cell membrane-derived platforms, the following limitations have seriously limited the commercialization potential: complex membrane composition, difficult batch difference control, inconvenient source cell expansion, To overcome these limitations, artificial cell membrane camouflage made from commercialized lipids and proteins was proposed in this work. Specifically, a biotinylated phospholipid which can serve as a lipid component and provide active sites (biotin) for antibody modification, and human serum albumin (HSA), which can effectively reduce certain blood protein adsorption, were applied simultaneously to endow our immunomagnetic platform with a new biological identity. Besides, making full use of the robust lipid and protein absorption ability of graphene nanosheets (GNs), the biomimetic cell membrane can be easily integrated into the magnetic core through simple lipid and protein solution incubation. Surprisingly, the resulting artificial cell membrane camouflaged immunomagnetic nanoparticles (AIMNPs) achieved high specificity (average capture efficiency 87.0%), good sensitivity (7 model CTCs per 0.5 mL) and an enhanced anti-nonspecific absorption ability (15-105 white blood cells per 1.5 mL) in both mimic and clinical blood samples.

摘要

精确且特异性的循环肿瘤细胞(CTC)分离受到血细胞和蛋白质的严重干扰。尽管一些基于细胞膜的平台已取得了令人满意的结果,但以下局限性严重限制了其商业化潜力:细胞膜成分复杂、批次差异难以控制、源细胞扩增不便。为克服这些局限性,本研究提出了由商业化脂质和蛋白质制成的人工细胞膜伪装方法。具体而言,将一种可作为脂质成分并为抗体修饰提供活性位点(生物素)的生物素化磷脂与人血清白蛋白(HSA)同时应用,HSA可有效减少某些血液蛋白的吸附,从而赋予我们的免疫磁珠平台新的生物学特性。此外,充分利用石墨烯纳米片(GNs)强大的脂质和蛋白质吸附能力,通过简单的脂质和蛋白质溶液孵育,可轻松将仿生细胞膜整合到磁芯中。令人惊讶的是,所得的人工细胞膜伪装免疫磁珠纳米颗粒(AIMNPs)在模拟血液样本和临床血液样本中均实现了高特异性(平均捕获效率87.0%)、良好的灵敏度(每0.5 mL中有7个模型CTC)以及增强的抗非特异性吸附能力(每1.5 mL中有15 - 105个白细胞)。

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