Lipid-DNAs as Solubilizers of mTHPC

Yun Liu; Jan Willem de Vries; Qing Liu; Alwin M Hartman; Gerhard D Wieland; Sebastian Wieczorek; Hans G Börner; Arno Wiehe; Eric Buhler; Marc C A Stuart; Wesley R Browne; Andreas Herrmann; Anna K H Hirsch

doi:10.1002/chem.201705206

Lipid-DNAs as Solubilizers of mTHPC

Chemistry. 2018 Jan 19;24(4):798-802. doi: 10.1002/chem.201705206. Epub 2017 Dec 18.

Authors

Yun Liu¹, Jan Willem de Vries², Qing Liu², Alwin M Hartman^{1

3}, Gerhard D Wieland⁴, Sebastian Wieczorek⁵, Hans G Börner⁵, Arno Wiehe⁴, Eric Buhler⁶, Marc C A Stuart^{1

7}, Wesley R Browne⁸, Andreas Herrmann², Anna K H Hirsch^{1

3

9}

Affiliations

¹ Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747, AG Groningen, The Netherlands.
² Department of Polymer Chemistry, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747, AG Groningen, The Netherlands.
³ Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Department of Drug Design and Optimization, Campus Building E8.1, 66123, Saarbrücken, Germany.
⁴ biolitec research GmbH, Otto-Schott-Strasse 15, 07745, Jena, Germany.
⁵ Laboratory for Organic Synthesis of Functional Systems, Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Strasse 2, 12489, Berlin, Germany.
⁶ Laboratoire Matière et Systèmes Complexes (MSC) UMR 7057, Université Paris Diderot-Paris 7, Bâtiment Condorcet, 75205, Paris cedex 13, France.
⁷ Department of Electron Microscopy, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747, AG Groningen, The Netherlands.
⁸ Molecular Inorganic Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747, AG Groningen, The Netherlands.
⁹ Department of Pharmacy, Medicinal Chemistry, Saarland University, Campus Building E8.1, 66123, Saarbrücken, Germany.

Abstract

Hydrophobic drug candidates require innovative formulation agents. We designed and synthesized lipid-DNA polymers containing varying numbers of hydrophobic alkyl chains. The hydrophobicity of these amphiphiles is easily tunable by introducing a defined number of alkyl chain-modified nucleotides during standard solid-phase synthesis of DNA using an automated DNA synthesizer. We observed that the resulting self-assembled micelles solubilize the poorly water-soluble drug, meta-tetra-hydroxyphenyl-chlorin (mTHPC) used in photodynamic therapy (PDT) with high loading concentrations and loading capacities. A cell viability study showed that mTHPC-loaded micelles exhibit good biocompatibility without irradiation, and high PDT efficacy upon irradiation. Lipid-DNAs provide a novel class of drug-delivery vehicle, and hybridization of DNA offers a potentially facile route for further functionalization of the drug-delivery system with, for instance, targeting or imaging moieties.

Keywords: amphiphiles; drug delivery; lipid-DNA; micelles; photodynamic therapy.