Next Article in Journal
Scaffolds Formed via the Non-Equilibrium Supramolecular Assembly of the Synergistic ECM Peptides RGD and PHSRN Demonstrate Improved Cell Attachment in 3D
Previous Article in Journal
Enzymatic Degradation of Poly(butylene succinate) Copolyesters Synthesized with the Use of Candida antarctica Lipase B
Previous Article in Special Issue
Dual Stimuli-Responsive P(NIPAAm-co-SPA) Copolymers: Synthesis and Response in Solution and in Films
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessArticle
Polymers 2018, 10(6), 689; https://doi.org/10.3390/polym10060689

Efficient Shielding of Polyplexes Using Heterotelechelic Polysarcosines

1
Department of Pharmacy, Ludwig-Maximilians-Universität (LMU) Munich, Pharmaceutical Biotechnology, Butenandtstrasse 5-13, D-81377 Munich, Germany
2
Institute of Organic Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, D-55128 Mainz, Germany
3
Graduate School Materials Science in Mainz, Staudinger Weg 9, 55128 Mainz, Germany
4
Nanosystems Initiative Munich, Schellingstraße 4, D-80799 Munich, Germany
*
Authors to whom correspondence should be addressed.
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)
View Full-Text   |   Download PDF [2042 KB, uploaded 20 June 2018]   |  

Abstract

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
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Polymers EISSN 2073-4360 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top