Barak Daniel, Engelberg Shira, Assaraf Yehuda G, Livney Yoav D
Lab of Biopolymers for Food & Health, Department of Biotechnology & Food Engineering, Technion, Israel Institute of Technology, Haifa 3200003, Israel.
The Fred Wyszkowski Cancer Research Lab, Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
Pharmaceutics. 2022 Aug 8;14(8):1650. doi: 10.3390/pharmaceutics14081650.
The leading cause of cancer mortality remains lung cancer (LC), of which non-small cell lung cancer (NSCLC) is the predominant type. Chemotherapy achieves only low response rates while inflicting serious untoward toxicity. Herein, we studied the binding and internalization of S15-aptamer (S15-APT)-decorated polyethylene glycol-polycaprolactone (PEG-PCL) nanoparticles (NPs) by various human NSCLC cell lines. All the NSCLC cell lines were targeted by S15-APT-decorated NPs. Confocal microscopy revealed variable levels of NP binding and uptake amongst these NSCLC cell lines, decreasing in the following order: Adenocarcinoma (AC) A549 cells > H2228 (AC) > H1299 (large cell carcinoma) > H522 (AC) > H1975 (AC). Flow cytometry analysis showed a consistent variation between these NSCLC cell lines in the internalization of S15-APT-decorated quantum dots. We obtained a temperature-dependent NP uptake, characteristic of active internalization. Furthermore, cytotoxicity assays with APT-NPs entrapping paclitaxel, revealed that A549 cells had the lowest IC50 value of 0.03 µM PTX (determined previously), whereas H2228, H1299, H522 and H1975 exhibited higher IC50 values of 0.38 µM, 0.92 µM, 2.31 µM and 2.59 µM, respectively (determined herein). Cytotoxicity was correlated with the binding and internalization of APT-NPs in the various NSCLC cells, suggesting variable expression of the putative S15 target receptor. These findings support the development of APT-targeted NPs in precision nanomedicine for individual NSCLC patient treatment.
癌症死亡的主要原因仍然是肺癌（LC），其中非小细胞肺癌（NSCLC）是主要类型。化疗仅能达到较低的缓解率，同时会带来严重的不良毒性。在此，我们研究了用S15适配体（S15-APT）修饰的聚乙二醇-聚己内酯（PEG-PCL）纳米颗粒（NPs）与各种人类NSCLC细胞系的结合及内化情况。所有NSCLC细胞系均被S15-APT修饰的NPs靶向。共聚焦显微镜显示这些NSCLC细胞系中NP的结合和摄取水平各不相同，顺序如下：腺癌（AC）A549细胞>H2228（AC）>H1299（大细胞癌）>H522（AC）>H1975（AC）。流式细胞术分析显示这些NSCLC细胞系在S15-APT修饰的量子点内化方面存在一致的差异。我们获得了与温度相关的NP摄取，这是主动内化的特征。此外，用包裹紫杉醇的APT-NPs进行细胞毒性试验，结果显示A549细胞的IC50值最低，为0.03 µM紫杉醇（先前测定），而H2228、H1299、H522和H1975的IC50值分别较高，为0.38 µM、0.92 µM、2.31 µM和2.59 µM（本文测定）。细胞毒性与各种NSCLC细胞中APT-NPs的结合及内化相关联，表明假定的S15靶受体表达存在差异。这些发现支持了在精准纳米医学中开发针对个体NSCLC患者治疗的APT靶向NPs。
