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Efficient Shielding of Polyplexes Using Heterotelechelic Polysarcosines

Department of Pharmacy, Ludwig-Maximilians-Universität (LMU) Munich, Pharmaceutical Biotechnology, Butenandtstrasse 5-13, D-81377 Munich, Germany
Institute of Organic Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, D-55128 Mainz, Germany
Graduate School Materials Science in Mainz, Staudinger Weg 9, 55128 Mainz, Germany
Nanosystems Initiative Munich, Schellingstraße 4, D-80799 Munich, Germany
Authors to whom correspondence should be addressed.
Polymers 2018, 10(6), 689;
Received: 28 May 2018 / Revised: 13 June 2018 / Accepted: 17 June 2018 / Published: 20 June 2018
(This article belongs to the Special Issue Hydrophilic Polymers)
Shielding agents are commonly used to shield polyelectrolyte complexes, e.g., polyplexes, from agglomeration and precipitation in complex media like blood, and thus enhance their in vivo circulation times. Since up to now primarily poly(ethylene glycol) (PEG) has been investigated to shield non-viral carriers for systemic delivery, we report on the use of polysarcosine (pSar) as a potential alternative for steric stabilization. A redox-sensitive, cationizable lipo-oligomer structure (containing two cholanic acids attached via a bioreducible disulfide linker to an oligoaminoamide backbone in T-shape configuration) was equipped with azide-functionality by solid phase supported synthesis. After mixing with small interfering RNA (siRNA), lipopolyplexes formed spontaneously and were further surface-functionalized with polysarcosines. Polysarcosine was synthesized by living controlled ring-opening polymerization using an azide-reactive dibenzo-aza-cyclooctyne-amine as an initiator. The shielding ability of the resulting formulations was investigated with biophysical assays and by near-infrared fluorescence bioimaging in mice. The modification of ~100 nm lipopolyplexes was only slightly increased upon functionalization. Cellular uptake into cells was strongly reduced by the pSar shielding. Moreover, polysarcosine-shielded polyplexes showed enhanced blood circulation times in bioimaging studies compared to unshielded polyplexes and similar to PEG-shielded polyplexes. Therefore, polysarcosine is a promising alternative for the shielding of non-viral, lipo-cationic polyplexes. View Full-Text
Keywords: shielding agent; polysarcosine; biodistribution; click-chemistry; lipopolyplex; nucleic acid carrier shielding agent; polysarcosine; biodistribution; click-chemistry; lipopolyplex; nucleic acid carrier
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MDPI and ACS Style

Klein, P.M.; Klinker, K.; Zhang, W.; Kern, S.; Kessel, E.; Wagner, E.; Barz, M. Efficient Shielding of Polyplexes Using Heterotelechelic Polysarcosines. Polymers 2018, 10, 689.

AMA Style

Klein PM, Klinker K, Zhang W, Kern S, Kessel E, Wagner E, Barz M. Efficient Shielding of Polyplexes Using Heterotelechelic Polysarcosines. Polymers. 2018; 10(6):689.

Chicago/Turabian Style

Klein, Philipp Michael, Kristina Klinker, Wei Zhang, Sarah Kern, Eva Kessel, Ernst Wagner, and Matthias Barz. 2018. "Efficient Shielding of Polyplexes Using Heterotelechelic Polysarcosines" Polymers 10, no. 6: 689.

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