Characterization of a library of vitamin A-functionalized polymethacrylate-based nanoparticles for siRNA delivery

Paul Klemm; Sophie Huschke; Marko Rodewald; Nadia Ehteshamzad; Mira Behnke; Xinyue Wang; Gizem Cinar; Ivo Nischang; Stephanie Hoeppener; Christine Weber; Adrian T. Press; Christiane Höppener; Tobias Meyer; Volker Deckert; Michael Schmitt; Jürgen Popp; Michael Bauer; Stephanie Schubert

doi:10.1039/D0PY01626H

Characterization of a library of vitamin A-functionalized polymethacrylate-based nanoparticles for siRNA delivery†

Paul Klemm,^ab Sophie Huschke,^bc Marko Rodewald,

^bde Nadia Ehteshamzad,^ab Mira Behnke,^ab Xinyue Wang,^e Gizem Cinar,

^ab Ivo Nischang,

^ab Stephanie Hoeppener,

^ab Christine Weber,

^ab Adrian T. Press,

^c Christiane Höppener,

^de Tobias Meyer,^d Volker Deckert,

^bdef Michael Schmitt,^de Jürgen Popp,^bde Michael Bauer^bc and Stephanie Schubert

*^bg

Author affiliations

* Corresponding authors

^a Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743 Jena, Germany

^b Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743 Jena, Germany
E-mail: stephanie.schubert@uni-jena.de

^c Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany

^d Leibniz Institute of Photonic Technology Jena, Member of Leibniz Health Technologies, Albert-Einstein-Strasse 9, 07745 Jena, Germany

^e Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Lessingstrasse 10, 07743 Jena, Germany

^f Institute for Quantum Science and Engineering (IQSE), Texas A&M University, College Station, TX 77843, USA

^g Institute of Pharmacy, Department of Pharmaceutical Technology and Biopharmacy, Friedrich Schiller University Jena, Lessingstrasse 8, Germany

Abstract

A 60-membered library of vitamin A-functionalized P(MMA-stat-DMAEMA)-b-PPEGMA block copolymers was synthesized by RAFT polymerization. The retinoic acid was coupled to hydroxyl groups present in the hydrophilic PPEGMA block. The polymers were investigated for their ability to encapsulate ribonucleic acids through nanoparticle (NP) formulation using the emulsion/solvent evaporation method. The localization of retinyl in surface-near regions of the NPs was indicated by surface enhanced Raman spectroscopy, and the interaction of the NPs with a retinol binding protein was investigated by an analytical ultracentrifuge. The systematic analysis of the NP library in terms of the encapsulation efficiency of the ribonucleic acids, the toxicity of the NPs, and the cellular uptake helped identifying suitable candidates for cellular internalization studies. The cell uptake was investigated by flow cytometry and fluorescence microscopy and reveals structure dependent uptake behavior of the examined particles.

Polymer Chemistry

Characterization of a library of vitamin A-functionalized polymethacrylate-based nanoparticles for siRNA delivery†

Abstract

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Characterization of a library of vitamin A-functionalized polymethacrylate-based nanoparticles for siRNA delivery

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