Hematogenous metastasis, the process of cancer cell migration from a primary to distal location via the bloodstream, typically leads to a poor patient prognosis. Selectin proteins hold promise in delivering drug-containing nanocarriers to circulating tumor cells (CTCs) in the bloodstream, due to their rapid, force-dependent binding kinetics. However, it is challenging to deliver such nanocarriers while avoiding toxic effects on healthy blood cells, as many possess ligands that adhesively interact with selectins. Herein, we describe a nanostructured surface to capture flowing cancer cells, while preventing human neutrophil adhesion. Microtube surfaces with immobilized halloysite nanotubes (HNTs) and E-selectin functionalized liposomal doxorubicin (ES-PEG L-DXR) significantly increased the number of breast adenocarcinoma MCF7 cells captured from flow, yet also significantly reduced the number of captured neutrophils. Neutrophils firmly adhered and projected pseudopods on surfaces coated only with liposomes, while neutrophils adherent to HNT-liposome surfaces maintained a round morphology. Perfusion of both MCF7 cells and neutrophils resulted in primarily cancer cell adhesion to the HNT-liposome surface, and induced significant cancer cell death. This work demonstrates that nanostructured surfaces consisting of HNTs and ES-PEG L-DXR can increase CTC recruitment for chemotherapeutic delivery, while also preventing healthy cell adhesion and uptake of therapeutic intended for CTCs.

中文翻译：

---

纳米结构表面靶向并杀死循环肿瘤细胞，同时排斥白细胞。

血行转移是癌细胞通过血流从原发位置迁移到远端位置的过程，通常会导致患者预后不良。由于其快速、依赖于力的结合动力学，选择素蛋白有望将含药物的纳米载体输送到血流中的循环肿瘤细胞 (CTC)。然而，在避免对健康血细胞产生毒性作用的同时递送此类纳米载体是具有挑战性的，因为许多具有与选择素粘附相互作用的配体。在此，我们描述了一种纳米结构表面来捕获流动的癌细胞，同时防止人类中性粒细胞粘附。具有固定化埃洛石纳米管 (HNT) 和 E-选择素功能化脂质体阿霉素 (ES-PEG L-DXR) 的微管表面显着增加了从流动中捕获的乳腺癌 MCF7 细胞的数量，但也显着减少了捕获的中性粒细胞的数量。中性粒细胞牢固地粘附并投射在仅涂有脂质体的表面上的伪足，而粘附在 HNT 脂质体表面的中性粒细胞保持圆形形态。MCF7 细胞和中性粒细胞的灌注主要导致癌细胞粘附到 HNT 脂质体表面，并诱导显着的癌细胞死亡。这项工作表明，由 HNT 和 ES-PEG L-DXR 组成的纳米结构表面可以增加用于化疗的 CTC 募集，