Abstract
Surface modification of nanocarriers offers the possibility of targeted drug delivery, which is of major interest in modern pharmaceutical science. Click-chemistry affords an easy and fast way to modify the surface with targeting structures under mild reaction conditions. Here we describe our current method for the post-preparational surface modification of multifunctional sterically stabilized (stealth) liposomes via copper-catalyzed azide–alkyne cycloaddition (CuAAC) and inverse electron demand Diels-Alder norbornene–tetrazine cycloaddition (IEDDA). We emphasize the use of these in a one-pot orthogonal reaction for deep investigation on stability and targeting of nanocarriers. As the production of clickable amphiphilic polymers is a limiting factor in most cases, we also describe our nanocarrier preparation technique called dual centrifugation, which enables the formulation of liposomes on a single-digit milligram scale of total lipid mass.
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References
Strebhardt K, Ullrich A et al (2008) Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat Rev Cancer 8:473–480
Holmberg E et al (1989) Highly efficient immunoliposomes prepared with a method which is compatible with various lipid compositions. Biochem Biophys Res Commun 175:1272–1278
Uster PS et al (1996) Insertion of poly(ethylene glycol) derivatized phospholipid into pre-formed liposomes results in prolonged in vivo circulation time. FEBS Lett 386:243–246
Gantert M et al (2009) Receptor-specific targeting with liposomes in vitro based on sterol-PEG(1300) anchors. Int J Pharm 469:168–178
Allen TM, Sapra P, Moase E (2002) Use of the post-insertion method for the formation of ligand-coupled liposomes. Cell Mol Biol Lett 7:889–894
Fritz T et al (2014) Click modification of multifunctional liposomes bearing hyperbranched polyether chains. Biomacromolecules 15:3114–3118
Bangham AD (1983) The liposome letters. Academic Press, New York
Bangham AD et al (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13:238–252
Hofmann AM et al (2010) Hyperbranched polyglycerol-based lipids via oxyanionic polymerization: toward multifunctional stealth liposomes. Biomacromolecules 11:568–574
Hofmann AM, Wurm F, Frey H (2011) Rapid access to polyfunctional lipids with complex architecture via oxyanionic ring-opening polymerization. Macromolecules 44:4648–4657
Müller SS et al (2013) Polyether-based lipids synthesized with an epoxide construction kit: multivalent architectures for functional liposomes. In: Scholz C, Kressler J (eds) Tailored polymer architectures for pharmaceutical and biomedical applications, chap. 2. American Chemical Society, Washington DC, pp 11–25
Papahadjopoulos D et al (1991) Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. Proc Natl Acad Sci U S A 88(24):11460–11464
Kronberg B et al (1990) Preparation and evaluation of sterically stabilized liposomes: colloidal stability, serum stability, macrophage uptake, and toxicity. J Pharm Sci 79(8):667–671
Allen TM et al (1995) Pharmacokinetics of long-circulating liposomes. Adv Drug Deliv Rev 16(2–3):257–284
Allen TM et al (1992) Stealth liposomes: an improved sustained release system for 1-β-D-arabinofuranosylcytosine. Cancer Res 52:2431–2439
Blume G, Cevs G (1990) Liposomes for the sustained drug release in vivo. Biochim Biophys Acta 1029(1):91–97
Fritz T, Voigt M et al (2016) Orthogonal click conjugation to the liposomal surface reveals the stability of the lipid anchorage as crucial for targeting. Chem Eur J 22(33):11578–11582
Himo F et al (2005) Copper(I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates. J Am Chem Soc 127:210–216
Rostovstev VV et al (2002) A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed 41(14):2596–2599
Turnoe CW, Christensen C, Meldal M (2002) Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J Org Chem 67(9):3057–3064
Agard NJ, Prescher J, Bertozzi CR (2004) A strain-promoted [3+2] azide-alkyne cycloaddition for covalent modification of biomolecules in living systems. J Am Chem Soc 126(46):15046–15047
Blackman ML, Royzen M, Fox JM (2008) The Tetrazine ligation: fast bioconjugation on inverse-electron-demand Diels-Alder reactivity. J Am Chem Soc 130:13518
Devaraj NK, Weissleder R, Hilderbrand SA (2008) Tetrazine-based cycloadditions: application to pretargeted live cell imaging. Bioconjugate Chem 19(12):2297–2299
Han H et al (2010) Development of a bioorthogonal and highly efficient conjugation method for quantum dots using tetrazine-norbornene cycloaddition. J Am Chem Soc 123(23):7838–7839
Massing U, Cicko S, Ziroli V (2008) Dual asymmetric centrifugation (DAC)—a new technique for liposome preparation. J Control Release 125(1):16–24
Hirsch M et al (2009) Preparation of small amounts of sterile siRNA-liposomes with high entrapping efficiency by dual asymmetric centrifugation (DAC). J Control Release 135(1):80–88
Acknowledgements
The Rotanta 400 dual centrifuge prototype was kindly provided by Andreas Hettich GmbH, Tuttlingen, Germany. The authors would like to thank the collaborative research center SFB 1066 (Project A7) by the German Research Foundation (DFG).
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Voigt, M., Fritz, T., Worm, M., Frey, H., Helm, M. (2019). Surface Modification of Nanoparticles and Nanovesicles via Click-Chemistry. In: Weissig, V., Elbayoumi, T. (eds) Pharmaceutical Nanotechnology. Methods in Molecular Biology, vol 2000. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9516-5_16
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DOI: https://doi.org/10.1007/978-1-4939-9516-5_16
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