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Article

Polymeric Nanoparticles Based on Tyrosine-Modified, Low Molecular Weight Polyethylenimines for siRNA Delivery

1
Rudolf-Boehm-Institute for Pharmacology and Toxicology, Faculty of Medicine, Clinical Pharmacology, Leipzig University, 04107 Leipzig, Germany
2
Faculty of Chemistry, Technical University Kaiserslautern, 67663 Kaiserslautern, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(11), 600; https://doi.org/10.3390/pharmaceutics11110600
Submission received: 29 September 2019 / Revised: 6 November 2019 / Accepted: 8 November 2019 / Published: 12 November 2019
(This article belongs to the Special Issue Drug Delivery of siRNA Therapeutics)

Abstract

A major hurdle for exploring RNA interference (RNAi) in a therapeutic setting is still the issue of in vivo delivery of small RNA molecules (siRNAs). The chemical modification of polyethylenimines (PEIs) offers a particularly attractive avenue towards the development of more efficient non-viral delivery systems. Here, we explore tyrosine-modified polyethylenimines with low or very low molecular weight (P2Y, P5Y, P10Y) for siRNA delivery. In comparison to their respective parent PEI, they reveal considerably increased knockdown efficacies and very low cytotoxicity upon tyrosine modification, as determined in different reporter and wildtype cell lines. The delivery of siRNAs targeting the anti-apoptotic oncogene survivin or the serine/threonine-protein kinase PLK1 (polo-like kinase 1; PLK-1) oncogene reveals strong inhibitory effects in vitro. In a therapeutic in vivo setting, profound anti-tumor effects in a prostate carcinoma xenograft mouse model are observed upon systemic application of complexes for survivin or PLK1 knockdown, in the absence of in vivo toxicity. We thus demonstrate the tyrosine-modification of (very) low molecular weight PEIs for generating efficient nanocarriers for siRNA delivery in vitro and in vivo, present data on their physicochemical and biological properties, and show their efficacy as siRNA therapeutic in vivo, in the absence of adverse effects.
Keywords: poly(ethylene) imine; PEI; RNA; siRNA delivery; tyrosine-modification; tumor xenograft poly(ethylene) imine; PEI; RNA; siRNA delivery; tyrosine-modification; tumor xenograft
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MDPI and ACS Style

Ewe, A.; Noske, S.; Karimov, M.; Aigner, A. Polymeric Nanoparticles Based on Tyrosine-Modified, Low Molecular Weight Polyethylenimines for siRNA Delivery. Pharmaceutics 2019, 11, 600. https://doi.org/10.3390/pharmaceutics11110600

AMA Style

Ewe A, Noske S, Karimov M, Aigner A. Polymeric Nanoparticles Based on Tyrosine-Modified, Low Molecular Weight Polyethylenimines for siRNA Delivery. Pharmaceutics. 2019; 11(11):600. https://doi.org/10.3390/pharmaceutics11110600

Chicago/Turabian Style

Ewe, Alexander, Sandra Noske, Michael Karimov, and Achim Aigner. 2019. "Polymeric Nanoparticles Based on Tyrosine-Modified, Low Molecular Weight Polyethylenimines for siRNA Delivery" Pharmaceutics 11, no. 11: 600. https://doi.org/10.3390/pharmaceutics11110600

APA Style

Ewe, A., Noske, S., Karimov, M., & Aigner, A. (2019). Polymeric Nanoparticles Based on Tyrosine-Modified, Low Molecular Weight Polyethylenimines for siRNA Delivery. Pharmaceutics, 11(11), 600. https://doi.org/10.3390/pharmaceutics11110600

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