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结合混合细胞膜修饰的磁性纳米颗粒和倒置微流控芯片用于原位 CTCs 的捕获和失活。

Combining hybrid cell membrane modified magnetic nanoparticles and inverted microfluidic chip for in situ CTCs capture and inactivation.

机构信息

State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, 2699 Qianjin Street, Changchun, 130012, China; Department of Cell Biology, College of Basic Medical Science, Jilin University, Changchun, 130021, China.

State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, 2699 Qianjin Street, Changchun, 130012, China.

出版信息

Biosens Bioelectron. 2024 Nov 1;263:116575. doi: 10.1016/j.bios.2024.116575. Epub 2024 Jul 15.

Abstract

Circulating tumor cells (CTCs) serve as crucial indicators for tumor occurrence, progression, and prognosis monitoring. However, achieving high sensitivity and high purity capture of CTCs remains challenging. Additionally, in situ capture and synchronous clearance hold promise as methods to impede tumor metastasis, but further exploration is needed. In this study, biomimetic cell membrane-coated magnetic nanoparticles (NPs) were designed to address the issue of nonspecific adsorption of capture probes by the immune system during blood circulation. Membranes from human breast cancer cells (tumor cell membranes, TMs) and leukocytes (white blood cell membranes, WMs) were extracted and fused to form a hybrid membrane (HM), which was further modified onto the surface of porous magnetic NPs loaded with indocyanine green (ICG). The incorporation of TM enhanced the material's target specificity, thus increasing capture efficiency, while WM coating reduced interference from homologous white blood cells (WBCs), further enhancing capture purity. Additionally, in conjunction with our novel inverted microfluidic chip, this work introduces the first use of polymer photonic crystals as the capture interface for CTCs. Besides providing an advantageous surface structure for CTC attachment, the 808 nm photonic bandgap effectively amplifies the 808 nm excitation light at the capture surface position. Therefore, upon capturing CTCs, the ICG molecules in the probes facilitate enhanced photothermal (PTT) and photodynamic (PDT) synergistic effects, directly inactivating the captured CTCs. This method achieves capture efficiency and purity exceeding 95% and permits in situ inactivation post-capture, providing an important approach for future research on impeding tumor metastasis in vivo.

摘要

循环肿瘤细胞(CTCs)是肿瘤发生、进展和预后监测的重要指标。然而,实现对 CTCs 的高灵敏度和高纯度捕获仍然具有挑战性。此外,原位捕获和同步清除被认为是阻止肿瘤转移的有前途的方法,但需要进一步探索。在这项研究中,设计了仿生细胞膜包裹的磁性纳米颗粒(NPs),以解决血液循环中免疫捕获探针的非特异性吸附问题。从人乳腺癌细胞(肿瘤细胞膜,TMs)和白细胞(白细胞细胞膜,WMs)中提取并融合形成杂交膜(HM),进一步修饰在负载吲哚菁绿(ICG)的多孔磁性 NPs 表面。TM 的加入增强了材料的靶向特异性,从而提高了捕获效率,而 WM 涂层减少了同源白细胞(WBCs)的干扰,进一步提高了捕获纯度。此外,结合我们的新型倒置微流控芯片,这项工作首次将聚合物光子晶体用作 CTCs 的捕获接口。除了为 CTC 附着提供有利的表面结构外,808nm 光子带隙还有效地放大了捕获表面位置的 808nm 激发光。因此,在捕获 CTCs 后,探针中的 ICG 分子促进了增强的光热(PTT)和光动力(PDT)协同效应,直接使捕获的 CTCs失活。该方法的捕获效率和纯度超过 95%,并允许捕获后原位失活,为未来研究体内阻止肿瘤转移提供了重要途径。

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