title: Synthesis and Characterization of Stimuli-Responsive Star-Like Polypept(o)ides: Introducing Biodegradable PeptoStars.
abstract: Star-like polymers are one of the smallest systems in the class of core crosslinked polymeric nanoparticles. This article reports on a versatile, straightforward synthesis of three-arm star-like polypept(o)ide (polysarcosine-block-polylysine) polymers, which are designed to be either stable or degradable at elevated levels of glutathione. Polypept(o)ides are a recently introduced class of polymers combining the stealth-like properties of the polypeptoid polysarcosine with the functionality of polypeptides, thus enabling the synthesis of materials completely based on endogenous amino acids. The star-like homo and block copolymers are synthesized by living nucleophilic ring opening polymerization of the corresponding N-carboxyanhydrides (NCAs) yielding polymeric stars with precise control over the degree of polymerization (Xn= 25, 50, 100), Poisson-like molecular weight distributions, and low dispersities (Đ = 1.06-1.15). Star-like polypept(o)ides display a hydrodynamic radius of 5 nm (μ2< 0.05) as determined by dynamic light scattering (DLS). While star-like polysarcosines and polypept(o)ides based on disulfide containing initiators are stable in solution, degradation occurs at 100 × 10-3m glutathione concentration. The disulfide cleavage yields the respective polymeric arms, which possess Poisson-like molecular weight distributions and low dispersities (Đ = 1.05-1.12). Initial cellular uptake and toxicity studies reveal that PeptoStars are well tolerated by HeLa, HEK 293, and DC 2.4 cells.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Holm
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weber
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.|Graduate School Materials Science in Mainz, Staudinger Weg 9, 55128, Mainz, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Heller
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.|Graduate School Materials Science in Mainz, Staudinger Weg 9, 55128, Mainz, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Klinker
authors.affiliation: Department of Nanobiomedicine/ENT, University Medical Center of Mainz, Langenbeckstr. 1, 55101, Mainz, Germany.
authors.forename: Dana
authors.initials: D
authors.lastname: Westmeier
authors.affiliation: Department of Nanobiomedicine/ENT, University Medical Center of Mainz, Langenbeckstr. 1, 55101, Mainz, Germany.
authors.forename: Dominic
authors.initials: D
authors.lastname: Docter
authors.affiliation: Department of Nanobiomedicine/ENT, University Medical Center of Mainz, Langenbeckstr. 1, 55101, Mainz, Germany.
authors.forename: Roland H
authors.initials: RH
authors.lastname: Stauber
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-Universität Mainz, Duesbergweg 10-14, 55128, Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Barz
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D063566:Biodegradable Plastics / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005978:Glutathione / Q000737:chemistry; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry
chemical_list: D000596:Amino Acids; D063566:Biodegradable Plastics; D010455:Peptides; D011108:Polymers; D005978:Glutathione
keywords: NCA polymerization; block copolypept(o)ides; polypept(o)ide stars; redox-sensitive polypept(o)ide stars; star polymers