Filtern
Erscheinungsjahr
Dokumenttyp
Schlagworte
- MALDI-TOF MS (2)
- Amphiphilic polymers (1)
- Cellular uptake (1)
- Fourier-transform infrared (1)
- Glycopolymer vesicle (1)
- MALDI (1)
- Metal-free crosslinking (1)
- Nanoparticles (1)
- Nanotechnology (1)
- Oligospiroketals (1)
The nucleophilic thiol–ene (thia-Michael) reaction between molecular rods bearing terminal thiols and bis-maleimides was investigated. The molecular rods have oligospiroketal (OSK) and oligospirothioketal (OSTK) backbones. Contrary to the expectations, cyclic oligomers were always obtained instead of linear rigid-rod polymers. Replacing the OS(T)K rods with a flexible chain yielded polymeric products, suggesting that the OS(T)K structure is responsible for the formation of cyclic products. The reason for the preferred formation of cyclic products is due to the presence of folded conformations, which have already been described for articulated rods.
Polysarcosine (M-n = 3650-20 000 g mol(-1), D similar to 1.1) was synthesized from the air and moisture stable N-phenoxycarbonyl-N-methylglycine. Polymerization was achieved by in situ transformation of the urethane precursor into the corresponding N-methylglycine-N-carboxyanhydride, when in the presence of a non-nucleophilic tertiary amine base and a primary amine initiator.
Due to the adsorption of biomolecules, the control of the biodistribution of nanoparticles is still one of the major challenges of nanomedicine. Poly(2-ethyl-2-oxazoline) (PEtOx) for surface modification of nanoparticles is applied and both protein adsorption and cellular uptake of PEtOxylated nanoparticles versus nanoparticles coated with poly(ethylene glycol) (PEG) and non-coated positively and negatively charged nanoparticles are compared. Therefore, fluorescent poly(organosiloxane) nanoparticles of 15 nm radius are synthesized, which are used as a scaffold for surface modification in a grafting onto approach.
With multi-angle dynamic light scattering, asymmetrical flow field-flow fractionation, gel electrophoresis, and liquid chromatography-mass spectrometry, it is demonstrated that protein adsorption on PEtOxylated nanoparticles is extremely low, similar as on PEGylated nanoparticles. Moreover, quantitative microscopy reveals that PEtOxylation significantly reduces the non-specific cellular uptake, particularly by macrophage-like cells. Collectively, studies demonstrate that PEtOx is a very effective alternative to PEG for stealth modification of the surface of nanoparticles.
The protein corona, which forms on the nanoparticle's surface in most biological media, determines the nanoparticles physicochemical characteristics. The formation of the protein corona has a significant impact on the biodistribution and clearance of nanoparticles in vivo. Therefore, the ability to influence the formation of the protein corona is essential to most biomedical applications, including drug delivery and imaging. In this study, we investigate the protein adsorption on nanoparticles with a hydrodynamic radius of 30 nm and a coating of thermoresponsive poly(2-isopropyl-2-oxazoline) in serum. Using multiangle dynamic light scattering (DLS) we demonstrate that heating of the nanoparticles above their phase separation temperature induces the formation of agglomerates, with a hydrodynamic radius of 1 µm. In serum, noticeably stronger agglomeration occurs at lower temperatures compared to serum-free conditions. Cryogenic transmission electron microscopy (cryo-TEM) revealed a high packing density of agglomerates when serum was not present. In contrast, in the presence of serum, agglomerated nanoparticles were loosely packed, indicating that proteins are intercalated between them. Moreover, an increase in protein content is observed upon heating, confirming that protein adsorption is induced by the alteration of the surface during phase separation. After cooling and switching the surface back, most of the agglomerates were dissolved and the main fraction returned to the original size of approximately 30 nm as shown by asymmetrical flow-field flow fractionation (AF-FFF) and DLS. Furthermore, the amounts of adsorbed proteins are similar before and after heating the nanoparticles to above their phase-separation temperature. Overall, our results demonstrate that the thermoresponsivity of the polymer coating enables turning the corona formation on nanoparticles on and off in situ. As the local heating of body areas can be easily done in vivo, the thermoresponsive coating could potentially be used to induce the agglomeration of nanoparticles and proteins and the accumulation of nanoparticles in a targeted body region.
As polypeptoids become increasingly popular, they present a more soluble and processable alternative to natural and synthetic polypeptides; the breadth of their potential functionality slowly comes into focus. This report analyzes the ability of an alkyne-functionalized polypeptoid, poly(N-propargyl glycine), to crosslink upon heating. The crosslinking process is analyzed by thermal analysis (differential scanning calorimetry and thermogravimetric analysis), Fourier-transform infrared, electron paramagnetic resonance, and solid-state NMR spectroscopy. While a precise mechanism cannot be confidently assigned, it is clear that the reaction proceeds by a radical mechanism that exclusively involves the alkyne functionality, which, upon crosslinking, yields alkene and aromatic products.
Ring-opening polymerization of N-substituted glycine N-carboxyanhydrides (NCAs) was applied to prepare a series of well-defined poly(N-C3 glycine)s (C3 = n-propyl, allyl, propargyl, and isopropyl), polypeptoids, with molecular weights in the range of 1.8–6.6 kg mol–1. Poly(N-isopropyl glycine), a previously unreported polypeptoid, could be obtained by bulk polymerization of the corresponding NCA in the melt. The samples were characterized by spectroscopy (NMR and FT-IR), size exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI–ToF MS). The polymers could be dispersed in water up to 20–40 g L–1; the poly(N-propargyl glycine) was not soluble in water. Turbidity measurements of the three water-soluble polypeptoids illustrated cloud point temperatures dependent on structural and electronic properties of the side chain. The cloud point temperatures were found to increase in the order C3 = n-propyl (15–25 °C) < allyl (27–54 °C) < isopropyl (47–58 °C). Long-term annealing of the aqueous solution of poly(N-{n-propyl} glycine) and poly(N-allyl glycine) above the cloud point temperature resulted in the formation of crystalline microparticles with melting points of 188–198 and 157–165 °C (differential scanning calorimetry, DSC), respectively, and rose bud type morphology (scanning electron microscopy, SEM).
Synthesis of terpene-poly(ethylene oxide)s by t-BuP4-promoted anionic ring-opening polymerization
(2012)
Terpene alcohols (menthol, retinol, cholesterol, and betulin) together with the phosphazene base t-BuP4 were used as initiating systems for anionic ring-opening polymerization of ethylene oxide. The polymerizations were conducted in a controlled manner with the initial molar ratio of t-BuP4 to hydroxyl groups of 0.01–0.2, yielding a series of biohybrid polymers comprising terpene entities and poly(ethylene oxide) (PEO) chains with low polydispersities and tunable compositions (57–87 wt% of PEO). Samples were characterized by NMR and UV/visible spectroscopy, MALDI-TOF mass spectrometry, and size exclusion chromatography; thermal properties were studied by differential scanning calorimetry. The concept of this study opens a new toolbox of terpene-based biohybrid polymers with variable properties and functions.
The self-assembly of double-hydrophilic poly(ethylene oxide)–poly(2-methyl-2-oxazoline) diblock copolymers in water has been studied. Isothermal titration calorimetry, small-angle X-ray scattering, and analytical ultracentrifugation suggest that only single polymer chains are present in solution. In contrast, light scattering and transmission electron microscopy detect aggregates with radii of ca. 100 nm. Pulsed field gradient NMR spectroscopy confirms the presence of aggregates, although only 2% of the polymer chains undergo aggregation. Water uptake experiments indicate differences in the hydrophilicity of the two blocks, which is believed to be the origin of the unexpected aggregation behavior (in accordance with an earlier study by Ke et al. [Macromolecules2009, 42, 5339–5344]). The data therefore suggest that even in double-hydrophilic block copolymers, differences in hydrophilicity are sufficient to drive polymer aggregation, a phenomenon that has largely been overlooked or ignored so far.