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Brief Report

Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy

1
Department of Oncology, School of Medicine and Barbara Ann Karmanos Institute, Wayne State University, Detroit, MI 48201, USA
2
Department of Pharmaceutical Sciences, School of Pharmacy, Wayne State University, Detroit, MI 48201, USA
3
Department of Pharmacy, Ludwig-Maximilians-Universität München, 81377 München, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Paola Luciani and Davide Brambilla
Molecules 2020, 25(8), 1994; https://doi.org/10.3390/molecules25081994
Received: 14 February 2020 / Revised: 16 April 2020 / Accepted: 17 April 2020 / Published: 24 April 2020
Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5′-3′ structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is critical for the repair of platinum-induced DNA damage and has been the subject of intense research efforts to identify small molecule inhibitors of its nuclease activity for the purpose of enhancing patient response to platinum-based chemotherapy. As an alternative to small molecule inhibitors, small interfering RNA (siRNA) has often been described to be more efficient in interrupting protein–protein interactions. The goal of this study was therefore to determine whether biocompatible nanoparticles consisting of an amphiphilic triblock copolymer (polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG)) and carrying siRNA targeted to ERCC1 and XPF made by microfluidic assembly are capable of efficient gene silencing and able to sensitize lung cancer cells to cisplatin. First, we show that our PEI-PCL-PEG micelleplexes carrying ERCC1 and XPF siRNA efficiently knocked down ERCC1/XPF protein expression to the same extent as the standard siRNA transfection reagent, Lipofectamine. Second, we show that our siRNA-carrying nanoparticles enhanced platinum sensitivity in a p53 wildtype model of non-small cell lung cancer in vitro. Our results suggest that nanoparticle-mediated targeting of ERCC1/XPF is feasible and could represent a novel therapeutic strategy for targeting ERCC1/XPF in vivo. View Full-Text
Keywords: lung cancer; cisplatin resistance; ERCC1; siRNA; nanoparticle; microfluidics lung cancer; cisplatin resistance; ERCC1; siRNA; nanoparticle; microfluidics
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MDPI and ACS Style

Feldmann, D.P.; Heyza, J.; Zimmermann, C.M.; Patrick, S.M.; Merkel, O.M. Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy. Molecules 2020, 25, 1994. https://doi.org/10.3390/molecules25081994

AMA Style

Feldmann DP, Heyza J, Zimmermann CM, Patrick SM, Merkel OM. Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy. Molecules. 2020; 25(8):1994. https://doi.org/10.3390/molecules25081994

Chicago/Turabian Style

Feldmann, Daniel P., Joshua Heyza, Christoph M. Zimmermann, Steve M. Patrick, and Olivia M. Merkel. 2020. "Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy" Molecules 25, no. 8: 1994. https://doi.org/10.3390/molecules25081994

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