Selective Targeting and Eradication of Various Human Non-Small Cell Lung Cancer Cell Lines Using Self-Assembled Aptamer-Decorated Nanoparticles.

Autor: Barak D; Lab of Biopolymers for Food & Health, Department of Biotechnology & Food Engineering, Technion, Israel Institute of Technology, Haifa 3200003, Israel., Engelberg S; Lab of Biopolymers for Food & Health, Department of Biotechnology & Food Engineering, Technion, Israel Institute of Technology, Haifa 3200003, Israel., Assaraf YG; The Fred Wyszkowski Cancer Research Lab, Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel., Livney YD; Lab of Biopolymers for Food & Health, Department of Biotechnology & Food Engineering, Technion, Israel Institute of Technology, Haifa 3200003, Israel.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2022 Aug 08; Vol. 14 (8). Date of Electronic Publication: 2022 Aug 08.
DOI: 10.3390/pharmaceutics14081650
Abstrakt: 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.
Databáze: MEDLINE
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