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Polymers in Medicine and Biology: 2015
September 14 – 17, 2015
Poster 1
Sonoma Valley, CA
Poly(phosphoester)s as shielding polymers: Investigations on the stealth
effect of PPEylated nanocarriers
Greta Beckera,b, Susanne Schöttlera, Tobias Steinbacha,b, Katharina Landfestera, Volker Mailändera,
Frederik R. Wurma
aMax-Planck-Institut für Polymerforschung, Ackermannweg 10, 55128 Mainz, Germany,
bGraduate School Material Science in Mainz, Staudinger Weg 9, 55128 Mainz, Germany.
corresponding author: [email protected]
PEGylation (the covalent attachment of poly(ethylene glycol)) is today’s gold standard for drug delivery
vehicles to reduce unspecific cell uptake, i.e. to establish a “stealth” effect. 1 However, PEG is not
biodegradable and recent studies have also pointed out hypersensitivity or antibody formation against
PEG.2 Another very interesting polymer class was never investigated with respect to the “stealth”
behavior: poly(phosphoester)s (PPEs).3,4 The chemical structure of PPEs is highly modular, they are
degradable and their degradation products and time can be adjusted by precise chemistry.5
Herein, the first investigation of the stealth behavior of fully degradable, water-soluble poly(ethyl
ethylene phosphate)s (PEEP) are presented. Model nanocarriers with diameters of 100nm have been
prepared and PEEPs of different molecular weights have been covalently coupled to their surface
(Scheme 1). The polymers were synthesized by controlled anionic ring-opening polymerization of a
cyclic phosphate, 2-ethoxy-2-oxo-1,3,2-dioxaphospholane (“ethyl ethylene phosphate”, EEP).6
Polymers with different degrees of polymerization and narrow molecular weight distributions (<1.1)
were generated. A combination of techniques allowed the determination of the number of polymer
chains attached to the nanocarriers, which were then investigated with respect to their cell uptake,
cytotoxicity, protein adsorption and protein corona composition and compared to PEGylated
nanocarriers (Fig. 1).
Scheme 1. Synthesis of PEEP and coupling to amino-functionalized nanocarriers.
Figure 1. Behavior of cellular uptake of nanocarriers depending on their surface modification.
References
1. F.M. Veronese, G. Pasut, Drug Discovery Today, 2005, 10, 1451.
2. T. Ishida, H. Kiwada, Biological & pharmaceutical bulletin 2013, 36, 889.
3. T. Steinbach, S. Ritz, F. R. Wurm ACS Macro Lett. 2014, 3, 244.
4. T. Steinbach, E. M. Alexandrino, F. R. Wurm, Polym. Chem. 2013, 4, 3800.
5. K. D. Troev, Polyphosphoesters: Chemistry and Application. Elsevier: 2012.
6. B. Clément, B. Grignard, L. Koole, C. Jérôme, P. Lecomte, Macromolecules 2012, 45, 4476.