Endolytic, pH-responsive HPMA-b-(L-Glu) copolymers synthesized via sequential aqueous RAFT and ring-opening polymerizations.

A facile synthetic pathway for preparing block copolymers with pH-responsive L-glutamic acid segments for membrane disruption is reported. Aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization was first used to prepare biocompatible, nonimmunogenic poly[N-(2-hydroxypropyl)methacrylamide]. This macro chain transfer agent (CTA) was then converted into a macroinitiator via simultaneous aminolysis and thiol-ene Michael addition using the primary amine substituted N-(3-aminopropyl)methacrylamide. This macroinitiator was subsequently utilized in the ring-opening polymerization of the N-carboxyanhydride monomer of γ-benzyl-L-glutamate. After deprotection, the pH-dependent coil-to-helix transformations of the resulting HPMA-b-(L-Glu) copolymers were monitored via circular dichroism spectroscopy. HPMA segments confer water solubility and biocompatibility while the L-glutamic acid repeats provide reversible coil-to-helix transitions at endosomal pH values (~5-6). The endolytic properties of these novel [HPMA-b-(L-Glu)] copolymers and their potential as modular components in drug carrier constructs was demonstrated utilizing red blood cell hemolysis and fluorescein release from POPC vesicles.

Stimuli-responsive peptide-based ABA-triblock copolymers: unique morphology transitions with pH.

We report the synthesis and solution characterization of poly(L-lysine)-b-poly(propylene oxide)-b-poly(L-lysine) (KPK) triblock copolymers with high lysine weight fractions (>75 wt%). In contrast to PK diblock copolymers in this composition range, KPK triblock copolymers exhibit morphology transitions as a function of pH. Using a combination of light-scattering and microscopy techniques, we demonstrate spherical micelle-vesicle and spherical micelle-disk micelle transitions for different K fractions. We interpret these morphology changes in terms of the energy penalty associated with folding the core P block to form a spherical micelle in relation to the interfacial curvature associated with different charged states of the K block.

Dynamic-covalent macromolecular stars with boronic ester linkages.

Macromolecular stars containing reversible boronic ester linkages were prepared by an arm-first approach by reacting well-defined boronic acid-containing block copolymers with multifunctional 1,2/1,3-diols. Homopolymers of 3-acrylamidophenylboronic acid (APBA) formed macroscopic dynamic-covalent networks when cross-linked with multifunctional diols. On the other hand, adding the diol cross-linkers to block copolymers of poly(N,N-dimethylacrylamide (PDMA))-b-poly(APBA) led to nanosized multiarm stars with boronic ester cores and PDMA coronas. The assembly of the stars under a variety of conditions was considered. The dynamic-covalent nature of the boronic ester cross-links allowed the stars to reconfigure their covalent structure in the presence of monofunctional diols that competed for bonding with the boronic acid component. Therefore, the stars could be induced to dissociate via competitive exchange reactions. The star formation-dissociation process was shown to be repeatable over multiple cycles.

Temperature- and pH-responsive self-assembly of poly(propylene oxide)-b-poly(lysine) block copolymers in aqueous solution.

A series of poly(propylene oxide)-b-poly(L-lysine) (PPO-PK) block copolymers were synthesized using Huisgen's 1,3-dipolar cycloaddition, and the solution self-assembly was studied using transmission electron microscopy, circular dichroism spectroscopy, and dynamic and static light scattering techniques. In contrast to previous studies of poly(lysine)-based block copolymers, PPO-PK exhibits a significant shift in the pH associated with the helix-coil transition of the poly(lysine) block, potentially a result of decreased hydrophobicity in the core PPO block. Given the proximity of the lower critical solution temperature of the PPO block, these materials exhibit both pH and temperature-responsive (i.e., "schizophrenic") self-assembly, the latter of which was interpreted in terms of changes in the second osmotic virial coefficient. Finally, the vesicle morphology obtained from these polymers was studied for the propensity in drug encapsulation and passive release.

Synthesis of thiol-clickable and block copolypeptide brushes via nickel-mediated surface initiated polymerization of α-amino acid N-carboxyanhydrides (NCAs).

We describe the synthesis of homo-, block, and clickable copolypeptide brushes from low surface area substrates using nickel-mediated surface-initiated polymerization of α-amino N-carboxyanhydrides.