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J. Pers. Med. 2018, 8(1), 4; https://doi.org/10.3390/jpm8010004

Novel PAMAM-PEG-Peptide Conjugates for siRNA Delivery Targeted to the Transferrin and Epidermal Growth Factor Receptors

1
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, 31080 Pamplona, Spain
2
Department of Pharmaceutical Chemistry, Laboratory of MacroMolecular Cancer Therapeutics (MMCT), University of Vienna, 1010 Vienna, Austria
3
Pharmaceutical Biotechnology, Center for NanoScience (CeNS), Ludwig-Maximilians-University (LMU) 80799 Munich, Germany
*
Author to whom correspondence should be addressed.
Received: 24 October 2017 / Revised: 19 December 2017 / Accepted: 27 December 2017 / Published: 9 January 2018
(This article belongs to the Special Issue Personalized Nanomedicine)
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Abstract

The transferrin (TfR) and epidermal growth factor receptors (EGFR) are known to be overexpressed on the surface of a wide variety of tumor cells. Therefore, the peptides B6 (TfR specific) and GE11 (targeted to the EGFR) were linked to the PAMAM (polyamidoamine) structure via a polyethylenglycol (PEG) 2 kDa chain with the aim of improving the silencing capacity of the PAMAM-based dendriplexes. The complexes showed an excellent binding capacity to the siRNA with a maximal condensation at nitrogen/phosphate (N/P) 2. The nanoparticles formed exhibited hydrodynamic diameters below 200 nm. The zeta potential was always positive, despite the complexes containing the PEG chain in the structure showing a drop of the values due to the shielding effect. The gene silencing capacity was assayed in HeLa and LS174T cells stably transfected with the eGFPLuc cassette. The dendriplexes containing a specific anti luciferase siRNA, assayed at different N/P ratios, were able to mediate a mean decrease of the luciferase expression values of 14% for HeLa and 20% in LS174T cells, compared to an unspecific siRNA-control. (p < 0.05). In all the conditions assayed, dendriplexes resulted to be non-toxic and viability was always above 75%. View Full-Text
Keywords: nanotechnology; cancer; gene therapy; cationic polymers; polyethylenglycol; gene silencing nanotechnology; cancer; gene therapy; cationic polymers; polyethylenglycol; gene silencing
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Urbiola, K.; Blanco-Fernández, L.; Ogris, M.; Rödl, W.; Wagner, E.; Tros de Ilarduya, C. Novel PAMAM-PEG-Peptide Conjugates for siRNA Delivery Targeted to the Transferrin and Epidermal Growth Factor Receptors. J. Pers. Med. 2018, 8, 4.

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