Tailoring the stealth properties of biocompatible polysaccharide nanocontainers.
Fundamental development of a biocompatible and degradable nanocarrier platform based on hydroxyethyl starch (HES) is reported. HES is a derivative of starch and possesses both high biocompatibility and improved stability against enzymatic degradation; it is used to prepare nanocapsules via the polyaddition reaction at the interface of water nanodroplets dispersed in an organic miniemulsion. The synthesized hollow nanocapsules can be loaded with hydrophilic guests in its aqueous core, tuned in size, chemically functionalized in various pathways, and show high shelf life stability. The surface of the HES nanocapsules is further functionalized with poly(ethylene glycol) via different chemistries, which substantially enhanced blood half-life time. Importantly, methods for precise and reliable quantification of the degree of functionalization are also introduced, which enable the precise control of the chemistry on the capsules' surface. The stealth properties of these capsules is studied both in-vitro and in-vivo. The functionalized nanocapsules serve as a modular platform for specific cell targeting, as they show no unspecific up-taken by different cell types and show very long circulating time in blood (up to 72 h).
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
Biao
B
Kang
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany; Department of Hematology, Medical Oncology, and Pneumology, University Medical, Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Patricia
P
Okwieka
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
Susanne
S
Schöttler
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
Oliver
O
Seifert
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
Roland E
RE
Kontermann
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
Klaus
K
Pfizenmaier
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
Anna
A
Musyanovych
Department of Hematology, Medical Oncology, and Pneumology, University Medical, Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Ralf
R
Meyer
Biontech AG, An der Goldgrube 12, 55131 Mainz, Germany; TRON - Translational Oncology at the University Medical Center of Johannes Gutenberg University Mainz, Langenbeckstr 1, 55131 Mainz, Germany.
Mustafa
M
Diken
Biontech AG, An der Goldgrube 12, 55131 Mainz, Germany; TRON - Translational Oncology at the University Medical Center of Johannes Gutenberg University Mainz, Langenbeckstr 1, 55131 Mainz, Germany.
Ugur
U
Sahin
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany; Department of Hematology, Medical Oncology, and Pneumology, University Medical, Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Volker
V
Mailänder
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany. Electronic address: wurm@mpip-mainz.mpg.de.
Frederik R
FR
Wurm
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
Katharina
K
Landfester
D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D003510:Cyclohexanes / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005434:Flow Cytometry; D006207:Half-Life; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000138:chemical synthesis / Q000737:chemistry; D007962:Leukocytes / Q000166:cytology; D008422:Materials Testing; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D014018:Tissue Distribution; D014867:Water / Q000737:chemistry
D001672:Biocompatible Materials; D003510:Cyclohexanes; D004337:Drug Carriers; D006895:Hydroxyethyl Starch Derivatives; D053769:Nanocapsules; D011134:Polysaccharides; D014867:Water; D011092:Polyethylene Glycols; C506365:Cyclohexane
Hydroxyl ethyl starch; Miniemulsion; Nanocarrier; PEGylation; Stealth effect