Selective Adhesion and Switchable Release of Breast Cancer Cells via Hyaluronic Acid Functionalized Dual Stimuli-Responsive Microgel Films.
Selective Adhesion and Switchable Release of Breast Cancer Cells via Hyaluronic Acid Functionalized Dual Stimuli-Responsive Microgel Films.
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DOI：
10.1021/acsabm.1c00586
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发表时间：
2021-07
影响因子：
4.7
通讯作者：
Melanie Schmidt;A. Franken;Dimitri Wilms;T. Fehm;H. Neubauer;Stephan Schmidt
中科院分区：
文献类型：
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作者：
Melanie Schmidt;A. Franken;Dimitri Wilms;T. Fehm;H. Neubauer;Stephan Schmidt
从液体活检样品中检测肿瘤细胞对于早期癌症诊断、恶性评估和治疗至关重要。在这项工作中，涂层的透明质酸（HA）功能化的双刺激响应聚（N-异丙基丙烯酰胺）（PNIPAM）微凝胶用于研究乳腺癌细胞结合的特异性，并评估细胞友好的释放机制，进一步诊断程序。微凝胶是通过直接沉淀聚合与胺轴承共聚单体和postfunctionalization与UV-不稳定的连接剂，共价结合HA的微凝胶网络。通过简单的物理吸附和退火建立了用于细胞结合的明确的微凝胶涂层。HA呈递PNIPAM微凝胶膜显示特异性粘附表达CD 44的乳腺癌细胞系（MDA-MB-231和MCF-7），其中粘附的增加与较高的CD 44表达和HA功能化相关。在冷却至低于PNIPAM微凝胶的较低临界溶液温度时，细胞可以被释放;然而，即使在长时间冷却和温和的机械搅拌后，仍有10-30%的细胞保留在表面上。在施加光刺激后，通过短的UV处理从微凝胶上切割HA单元来实现完全的细胞释放。由于相对简单的制备程序，这种双重响应的微凝胶膜可以被认为是有效的捕获，释放和诊断肿瘤细胞。
The detection of tumor cells from liquid biopsy samples is of critical importance for early cancer diagnosis, malignancy assessment, and treatment. In this work, coatings of hyaluronic acid (HA)-functionalized dual-stimuli responsive poly(N-isopropylacrylamide) (PNIPAM) microgels are used to study the specificity of breast cancer cell binding and to assess cell friendly release mechanisms for further diagnostic procedures. The microgels are established by straightforward precipitation polymerization with amine bearing comonomers and postfunctionalization with a UV-labile linker that covalently binds HA to the microgel network. Well-defined microgel coatings for cell binding are established via simple physisorption and annealing. The HA-presenting PNIPAM microgel films are shown to specifically adhere CD44 expressing breast cancer cell lines (MDA-MB-231 and MCF-7), where an increase in adhesion correlates with higher CD44 expression and HA functionalization. Upon cooling below the lower critical solution temperature of PNIPAM microgels, the cells could be released; however, 10-30% of the cells still remained on the surface even after prolonged cooling and mild mechanical agitation. A complete cell release is achieved after applying the light stimulus by short UV treatment cleaving HA units from the microgels. Owing to the comparatively straightforward preparation procedures, such dual-responsive microgel films could be considered for the effective capture, release, and diagnostics of tumor cells.