Preparation of hybrid triple‐stimuli responsive nanogels based on poly(L‐histidine)

Abstract

A series of novel multi‐responsive disulfide cross‐linked polypeptide nanogels has been synthesized by a one‐step ring‐opening polymerization process. The pH‐responsive core of the prepared nanogels was based on poly(L‐histidine), the difunctional N‐carboxy anhydride of l‐cystine (l‐Cys‐NCA) was used as a reduction‐cleavable cross‐linking agent, while the outer hydrophilic corona was comprised of a poly(ethylene oxide) block. Extensive molecular characterization studies were conducted in order to confirm the formation of the desired polymeric nanostructures and also to prove their responsiveness to external stimuli within the physiological values of healthy and cancer tissues. Furthermore, the disruption of the disulfide‐bond linkages between the polymeric chains was achieved by the presence of the reductive tripeptide glutathione (GSH), leading to size variations that were monitored by dynamic light scattering (DLS) and size‐exclusion chromatography (SEC). “Stealth” properties of the formed nanostructures were examined by zeta potential measurements. The described nanogels are clearly promising candidates for drug delivery applications. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1278–1288

Poly(Pentafluorophenyl Methacrylate)‐Based Nano‐Objects Developed by Photo‐PISA as Scaffolds for Post‐Polymerization Functionalization

“…This size increase corresponds to an initial swelling of the particles; over further time, the particles gradually degraded (Figure B inset). Similar behavior has also been reported in the literature . In stark contrast, EDA cross‐linked P1 particles did not respond to either concentration of GSH over the timescale of the experiment, as expected for EDA, which does not contain a disulfide bond therefore, treatment with GSH yielded no apparent response.…”

Synthesis and UCST-type phase behavior of polypeptide with alkyl side-chains in alcohol or ethanol/water solvent mixtures

“…They can be prepared in large‐scale by ring‐opening polymerization (ROP) from N ‐carboxyanhydride (NCA) monomers . While significant progress has been made on stimuli‐responsive polypeptides, UCST‐type thermoresponsive polypeptides in organic media has been less investigated . Moreover, UCST‐type phase behaviors of polypeptide in a binary solvent mixture have never been reported yet.…”

A Comprehensive Outlook of Synthetic Strategies and Applications of Redox‐Responsive Nanogels in Drug Delivery

“…The synthesis of well‐defined polypeptide architectures via ROP of N ‐carboxyanhydride (NCA) has received increasing attention during the last decade . Several reports have been published depicting the synthesis of micelles, vesicles, and nanogels by controlled ROP of NCAs . Mechanism of ROP (normal amine mechanism, NAM) (Figure B), involves the attack of a primary amine (nucleophile) to initiate polymerization of NCA leading to the formation of a polypeptide, whose molecular weight can be controlled by regulating NCA to amine ratio.…”