Polypeptide Block Research Articles

Disulfide‐centered star‐shaped polypeptide‐PEO block copolymers for reduction‐triggered drug release

ABSTRACTDisulfide‐centered star‐shaped poly(ε‐benzyloxycarbonyl‐l‐lysine)‐b‐poly(ethylene oxide) block copolymers (i.e., A2B4 type Cy‐PZlys‐b‐PEO) were synthesized by the combination of ring‐opening polymerization and thiol‐yne chemistry. Their molecular structures and physical properties were characterized in detail by FTIR, 1H NMR, gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, and polarized optical microscope. Despite mainly exhibiting an α‐helix conformation, the inner PZlys blocks within copolymers greatly prohibited the crystallinity of the outer PEO blocks and presented a liquid crystal phase transition behavior in solid state. These block copolymers Cy‐PZlys‐b‐PEO self‐assembled into nearly spherical micelles in aqueous solution, which had a hydrophobic disulfide‐centered PZlys core surrounded by a hydrophilic PEO corona. As monitored by means of DLS and TEM, these micelles were progressively reduced to smaller micelles in 10 mM 1,4‐dithiothreitol at 37 °C and finally became ones with a half size, demonstrating a reduction‐sensitivity. Despite a good drug‐loading property, the DOX‐loaded micelles of Cy‐PZlys‐b‐PEO exhibited a reduction‐triggered drug release profile with an improved burst‐release behavior compared with the linear counterpart. Importantly, this work provides a versatile strategy for the synthesis of the disulfide‐centered star‐shaped polypeptide block copolymers potential for intracellular glutathione‐triggered drug delivery systems. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2000–2010

Organometallic–Polypeptide Diblock Copolymers: Synthesis by Diels–Alder Coupling and Crystallization-Driven Self-Assembly to Uniform Truncated Elliptical Lamellae

This paper reports a new synthetic strategy for the preparation of polyferrocenylsilane (PFS) block copolymers (BCPs), by conjugation of two independently prepared homopolymers using Diels–Alder cycloaddition. The PFS blocks were synthesized by photocontrolled ring-opening polymerization, yielding polymers with a cyclopentadienyl end group that serves as a diene in the conjugation reaction. In this initial study we focused on the synthesis of organometallic–polypeptide block copolymers PFS-b-PBLG (PBLG = poly(γ-benzyl-l-glutamate) using PBLG polymers with a terminal maleimide attached by one-step postpolymerization modification. Five PFS-b-PBLG copolymers with different degrees of polymerization were synthesized and purified by a series of selective precipitations. The self-assembly of these samples was studied in N,N-dimethylformamide, a solvent selective for PBLG. The BCPs with a PFS block longer than the PBLG block after annealing at 90 °C formed highly uniform platelet micelles with a truncated elliptical shape. Experiments at 75 °C showed that disordered elongated structures formed initially, with fiber-like protrusions from the ends. Over time, the structures became shorter and wider, evolving into uniform truncated elliptical micelles. The process was monitored by X-ray diffraction (XRD) measurements and by 1H NMR spectroscopy. AFM analysis showed that the micelles were flat and that their thickness increased with the overall chain length of the BCP. Self-assembly of these BCPs in the presence of PFS homopolymer led to formation of flower-like mesostructures consisting of stacks of lamellar petals.

Self-assembly behavior of rod–coil–rod polypeptide block copolymers

Self-assembly behavior of rod–coil–rod poly(γ-benzyl-l-glutamate)-b-poly(ethylene glycol)-b-poly(γ-benzyl-l-glutamate) (PBLG-b-PEG-b-PBLG) triblock copolymers with various PBLG block lengths in aqueous solution was investigated. The PBLG-b-PEG-b-PBLG triblock copolymers are able to self-assemble into vesicles when PBLG block length is relatively short. Meanwhile, the initial polymer concentration was found to have influence on the self-assembly. Giant vesicles can be observed when the initial concentration is high. Dissipative particle dynamics (DPD) simulations about the vesicles revealed that the rigid rod blocks could be aligned parallelly with each other to form the monolayer vesicles wall. When the PBLG block length in the PBLG-b-PEG-b-PBLG triblock copolymers increases, the aggregate morphologies were observed to transform from vesicles to spherical micelles. Based on the experimental and simulation results, we proposed a possible mechanism of the morphological transitions of the rod–coil–rod triblock copolymer aggregates.

Characterization of hybrid copolymer containing thermosensitive and polypeptide blocks by thermogravimetric analysis

Thermogravimetric studies of polypeptide-based hybrid copolymer (PNIPAm-g-PEG)-b-PLys in a flow of nitrogen were carried out at four rates of linear increase of the temperature. The kinetics and mechanism of the degradation process were evaluated from the TG data using the iso-conversional calculation procedure of Kissinger–Akahira–Sunose recommended by the ICTAC kinetics committee. It is very important to determine the most probable function of the mechanism, because the kinetic parameters of the process depend on its selection. In this respect, the iso-conversion calculation procedure turned out to be the most appropriate one. In the present work, the kinetic triplet (E, A and the shape of the most appropriate f(α)-function) of this process, as well as the kinetic parameters for the formation of the activated complex from the reagent, was calculated. All the calculations were performed using programs developed by us.

Synthesis of Hyperbranched Polypeptide and PEO Block Copolymer by Consecutive Thiol-Yne Chemistry

Hyperbranched poly(ε-benzyloxycarbonyl-L-lysine) (HPlys) with multiple alkyne peripheries was synthesized through the click polycondensation of an AB2 type Plys macromonomer with α-thiol and ω-alkyne terminal groups (thiol is the A unit, and each π bond in alkyne is the B unit), and the resulting HPlys was further conjugated with thiol-termined poly(ethylene oxide) (PEO) to generate HPlys-b-PEO block copolymer by consecutive thiol-yne chemistry. Their molecular structures and physical properties were characterized in detail by FT-IR, (1)H NMR, gel permeation chromatography, differential scanning calorimetry, wide-angle X-ray diffraction, and polarized optical microscopy. HPlys and HPlys-b-PEO mainly assumed an α-helix conformation similar to the linear precursors, while the liquid crystalline phase transition of Plys segment disappeared within HPlys and HPlys-b-PEO. HPlys-b-PEO self-assembled into nearly spherical micelles in aqueous solution, while it gave a 5-fold lower critical aggregation concentration (8.9 × 10(-3) mg/mL) than a linear counterpart (4.5 × 10(-2) mg/mL), demonstrating a dendritic topology effect. Compared with a linear counterpart, HPlys-b-PEO gave a higher drug-loading capacity and efficiency for the anticancer drug doxorubicin (DOX) and a slower drug-release rate with an improved burst-release profile, enabling them useful for drug delivery systems. Importantly, this work provides a versatile strategy for the synthesis of hyperbranched polypeptides and related block copolymers by utilizing thiol-yne chemistry.

Synthesis of Polypeptide Block Copolymer Hybrids by the Combination of N‐Carboxyanhydride Polymerization and RAFT

The synthesis of hybrid bioconjugates via the ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs) using a synthetic macroinitiator is described. Poly(n-butyl acrylate), polystyrene, and poly(N-isopropyl acrylamide) are synthesized (polydisperity index,Đ < 1.1) using reversible addition-fragmentation chain transfer (RAFT) as the synthetic tool. A phthalimidomethyl trithiocarbonate RAFTchain transfer agentis used to prepare well-defined, end-functional polymers, which after deprotection result in amine terminal macroinitiators. The subsequent initiating systems could successfully be chain extended with ε-benzyloxycarbonyl-l-lysine or γ-benzyl-l-glutamate as the NCAs to produce a library of polymer-polypeptide conjugates. In doing so, a novel procedure for directly synthesizing bioconjugates via a non-modular route without the need for excessive purification and isolation steps is described.

Self-reinforced endocytoses of smart polypeptide nanogels for “on-demand” drug delivery

The pH and reduction dual-responsive polypeptide nanogels with self-reinforced endocytoses were prepared through ring-opening polymerization of l-glutamate N-carboxyanhydrides, deprotection of benzyl group and subsequent quaternization reaction between γ-2-chloroethyl-l-glutamate unit in polypeptide block and 2,2′-dithiobis(N,N-dimethylethylamine). The nanogels were revealed to exhibit smart pH and reduction dual-responsiveness, and excellent biocompatibilities, which expressed great potential as antitumor drug nanocarriers. Doxorubicin (DOX) as a model antitumor drug was loaded into nanogels through dispersion. DOX-loaded nanogels displayed a stable core-cross-linked structure under normal physiological condition (pH7.4), while rapidly releasing the payloads in the mimicking endosomal (pH5.3), tumor tissular (pH6.8) or intracellular reductive microenvironments (10.0mM glutathione). Confocal fluorescence microscopy demonstrated that DOX-loaded nanogels could deliver DOX into HepG2 cells (a human hepatoma cell line) more efficiently than the parent DOX-loaded micelle and free DOX. The enhanced cellular internalizations of DOX-loaded nanogels were more significant under tumor tissular acidic condition (pH6.8) ascribed to the quaternary ammonium groups in the cores. In addition, DOX-loaded nanogels exhibited improved in vitro and in vivo antitumor activities, and in vivo securities compared with DOX-loaded micelle and free DOX. These excellent features of the smart nanogels with quaternary ammonium groups were endowed with a bright prospect for intracellular targeting antitumor drug delivery.

Recent developments in polymer–block–polypeptide and protein–polymer bioconjugate hybrid materials

In the last few years, polymer bioconjugates have been shown to be useful in many emerging areas of materials science. Consequently, the synthesis of polymer bioconjugates has suddenly become a central topic in polymer chemistry. The versatility and robust nature of modern synthetic methods such as controlled radical polymerisation (CLRP),1Abbreviations: AGET, activators generated by electron transfer; AM, amine mechanism; AMM, activated monomer mechanism; ATRP, atom-transfer radical polymerisation; BLG, β-benzyl-L-glutamate; Boc, butylcarbonate; BSA, bovine serum albumin; CLRP, controlled radical polymerisation; CTAs, chain-transfer agents; DCC, dicyclohexylcarbodiimide; DLS, dynamic light scattering; DMAP, dimethylaminopyridine; DSC, differential scanning calorimetry; DMAEMA, dimethylaminoethyl methacrylate; FT-IR, Fourier-transform infrared; GFP, green fluorescent protein; GPC, gel permeation chromatography; HMA, hostasol methacrylate; His, histidine; HO−EbiB, 2-hydroxyethyl 2-bromoisobutyrate; HO−POEOMA, hydroxy-functionalised poly(oligo(ethylene oxide) monomethyl ether methacrylate); HRP, horseradish peroxidase; LCST, lower critical solution temperature; MePEG α-SPA, monomethoxy poly(ethylene glycol)-succinimidyl propionate; MW, molecular weight; n-BuA, butyl acrylate; NAM, N-acryloylmorpholine; NCAs, N-carboxyanhydrides; NHS, N-hydroxysuccinimidyl; NMP, nitroxide-mediated radical polymerisation; NMR, nuclear magnetic resonance; N-TMS, N-trimethylsilyl; PAGE, polyacrylamide gel electrophoresis; PBLA, poly(β-benzyl-L-aspartate); PBLG, poly(γ-benzyl-L-glutamate); PBS, phosphate-buffered saline; PDI, polydispersity index; PDS, pyridyl disulphide; PEG, poly(ethylene glycol); PEGA, poly(ethylene glycol) methyl ether acrylate; PEGMA, poly(ethylene glycol) methylether methacrylate; p(HEMA), poly(2-hydroxyethyl methacrylate); pHPMA, poly(N-(2-hydroxypropyl)methacrylamide); PMA, poly(methyl acrylate); pNIPAM, poly(N-isopropylacrylamide); PS, polystyrene; PyBOP, benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate; PZLL, poly(ε-carbobenzyloxy-L-lysine); RAFT, reversible addition-fragmentation chain-transfer polymerisation; rh–GH, recombinant human growth hormone; RMA, rhodamine methacrylate; ROP, ring-opening polymerisation; sCT, salmon calcitonin; SDS-PAGE, sodium dodecyl sulphate PAGE; SPPS, solid-phase supported synthesis; t-BA, tert-butyl acrylate; TCEP, tris(2-carboxyethyl)phosphine; THF, tetrahydrofuran; TMB, 3,3′,5,5′-tetramethylbenzidine; VLP, virus-like particle.1 ring-opening polymerisation (ROP), and ‘click’ chemistry make them excellent tools for the preparation of tailor-made polymer bioconjugates. CLRP in combination with other techniques has been shown to be a mature technology for building tailor-made block copolymers and protein–polymer conjugates with a wide range of applications, especially in biomedical domains. This review describes the recent advances and progress in the rapidly expanding field of bioconjugation, outlining the work performed up to 2012.

Endocytosis and Intracellular Trafficking Properties of Transferrin-Conjugated Block Copolypeptide Vesicles

Block polypeptides are an emerging class of materials that have the potential to be used in many biomedical applications, including the field of drug delivery. We have previously developed a negatively charged block copolypeptide, poly(L-glutamate)60-b-poly(L-leucine)20 (E60L20), which forms spherical vesicles in aqueous solution. Since these vesicles are negatively charged, they are minimally toxic toward cells. However, the negative charge also inhibits these vesicles from effectively being internalized by cells, which can be problematic as many therapeutics have intracellular targets. To overcome this limitation of the E60L20 vesicles, transferrin (Tf) was conjugated onto the vesicle surface, since the receptor for Tf is overexpressed on cancer cells. The enhanced uptake of the Tf-conjugated vesicle was verified through confocal microscopy. Furthermore, endocytosis and immunostaining experiments confirmed that the Tf conjugated on the vesicle surface plays a critical role in the internalization and subsequent intracellular trafficking behavior of the vesicles.

Self-Assembly of Elastin–Mimetic Double Hydrophobic Polypeptides

We have constructed a novel class of "double-hydrophobic" block polypeptides based on the hydrophobic domains found in native elastin, an extracellular matrix protein responsible for the elasticity and resilience of tissues. The block polypeptides comprise proline-rich poly(VPGXG) and glycine-rich poly(VGGVG), both of which dehydrate at higher temperature but form distinct secondary structures, β-turn and β-sheet respectively. In water at 45 °C, the block polypeptides initially assemble into nanoparticles rich in β-turn structures, which further connect into long (>10 μm), beaded nanofibers along with the increase in the β-sheet content. The nanofibers obtained are well-dispersed in water, and show thermoresponsive properties. Polypeptides comprising each block component assemble into different morphologies, showing that the conjugation of poly(VPGXG) and poly(VGGVG) plays a role for beaded fiber formation. These results may provide innovative ideas for designing peptide-based materials but also opportunities for developing novel materials useful for tissue engineering and drug delivery systems.

The effect of alkyl side groups on the secondary structure and crystallization of poly(ethylene glycol)-block-polypeptide copolymers

The solid state and melt nanoscale structures of a series of poly(ethylene glycol)-block-poly(γ-alkyl-l-glutamate)s (PEG-b-PALG) copolymers bearing different alkyl side groups, i.e., n-butyl, n-hexyl, n-octyl, and n-dodecyl, have been investigated in the present work. An interesting effect of alkyl side groups on the secondary conformation of polypeptide block, crystallization of PEG segments and morphology of the copolymers was observed. With increasing the length of alkyl side groups or raising the temperature, the predominant secondary structure gradually changed from α-helix to β-sheet conformation. Differential scanning calorimetry, wide-angle X-ray diffraction analysis and polarized optical microscopy indicated that the crystallization and morphology of PEG segments were markedly restricted by the polypeptide block. Therefore, the alkyl side groups not only exhibited significant influence on the conformation of polypeptide block, but also affected the crystallization of PEG segments. The secondary structure, crystallization and spherulite morphology of these synthetic biomaterials, which were significantly influenced by alkyl side groups, may play an important role in their physicochemical properties, such as self-assembly, as well as in some biomedical applications.

Versatile Biofunctionalization of Polypeptide-Based Thermosensitive Hydrogels via Click Chemistry

In this study, we report thermosensitive hydrogels based on poly(ethylene glycol)-block-poly(γ-propargyl-l-glutamate) (PEG-PPLG). (13)C NMR spectra, DLS, and circular dichroism spectra were employed to study the mechanism of the sol-gel phase transition. Mouse fibroblast L929 cells were encapsulated and cultured within the hydrogel matrices, and the encapsulated cells were shown to be highly viable in the gel matrices, suggesting that the hydrogels have excellent cytocompatibilities. The mass loss of the hydrogels in vitro was accelerated by the presence of proteinase K compared to the control group. In vivo biocompatibility studies revealed that the in situ formed gels in the subcutaneous layer last for ∼21 days, and H&E staining study suggested acceptable biocompatibility of our materials in vivo. The presence of alkynyl side groups in the PEG-PPLG copolymers allowed convenient further functionalization with azide-modified bioactive molecules, such as biotin and galactose. The biofunctionalized PEG-polypeptide block copolymers showed sol-gel phase transitions similar to the parent copolymers. Interestingly, the incorporation of galactose groups into the hydrogels was found to improve cell adhesion, likely due to the adsorption of fibronectin (FN) in cell-extracellular matrix (ECM). Because bioactive materials have shown unique advantages in biomedical applications, especially tissue engineering and regenerative medicine applications, we believe our novel functionalizable thermosensitive hydrogels have potential to serve as a versatile platform for the development of new biofunctional materials, for example, bioadhesive and bioresponsive hydrogels.

Stimuli responsive synthetic polypeptides derived from N-carboxyanhydride (NCA) polymerisation

The progress in NCA polymerisation combined with advanced orthogonal functionalization techniques as well as the integration with other controlled polymerisation techniques significantly widened the scope of polypeptide building blocks in a variety of material designs. Well-defined synthetic stimuli-responsive polypeptides ("smart" polypeptides) with incorporated different functionalities have been extensively explored over the past decades. Their significant potential lies in the fact that they combine natural and synthetic elements both contributing to their properties. These novel materials have potential applications in biomedicine and biotechnology including tissue engineering, drug delivery and biodiagnostics. Responsive polypeptides are capable of undergoing conformational changes and phase transition accompanied by variations in the chemical and physical changes of the polypeptides in response to an external stimulus such as biologically relevant species (i.e. biomolecules), the environment (i.e. temperature, pH), irradiation with light or exposure to a magnetic field. In this review, the recent developments including synthetic strategies and applications of synthetic stimuli-responsive homo- and block polypeptides are reviewed.

Self-assembled structures from PEGylated polypeptide block copolymers synthesized using a combination of ATRP, ROP, and click chemistry

In this study, we used a combination of atom transfer radical polymerization, ring opening polymerization, and click chemistry to synthesize new PEGylated polypeptide block copolymers of polystyrene-b-poly(γ-propargyl-L-glutamate-g-ethylene oxide) [PS-b-(PPLG-g-MEO2)]. We employed Fourier transform infrared spectroscopy and wide-angle X-ray diffraction (WAXD) to determine the secondary structures of the α-helical conformations of these PEGylated polypeptide block copolymers in the solid state, and circular dichroism spectroscopy to characterize them in solution. Hierarchical self-assembly of the PS-b-(PPLG-g-MEO2) diblock copolymers in the bulk state (characterized using WAXD, small-angle X-ray scattering, and transmission electron microscopy) led to the formation of lamellar structures as a result of microphase separation of the diblock copolymers; the hexagonal cylinder packing nanostructure featured α-helical conformations of PEGylated polypeptide segments, which were oriented perpendicular to the director of the lamellar structure formed by the diblock copolymers. We obtained a range of micellar structures from the PS-b-(PPLG-g-MEO2) diblock copolymer in DMF (common solvent) upon the addition of selective solvents (H2O or MeCN). We observed only spherical micelles from the PS-b-(PPLG-g-MEO2) diblock copolymer in DMF–MeCN systems at all MeCN compositions. The micelle structures changed, however, from spherical structures to long wormlike, vesicles, and large compound micelles in the DMF–H2O system upon increasing the content of water. These different morphology transformations arose as a result of very different PS–solvent (H2O or MeCN) interaction parameters.

Cationic, helical polypeptide-based gene delivery for IMR-90 fibroblasts and human embryonic stem cells

Diblock copolymers consisting of poly(ethylene glycol)-block-poly(γ-4-(((2-(piperidin-1-yl)ethyl)amino)methyl)benzyl-L-glutamate) (PEG-b-PVBLG-8) were synthesized and evaluated for their ability to mediate gene delivery in hard-to-transfect cells like IMR-90 human fetal lung fibroblasts and human embryonic stem cells (hESCs). The PEG-b-PVBLG-8 contained a membrane-disruptive, cationic, helical polypeptide block (PVBLG-8) for complexing with DNA and a hydrophilic PEG block to improve the biocompatibility of the gene delivery vehicle. The incorporation of PEG effectively reduced the toxicity of the helical PVBLG-8 block without dramatically compromising the polymer's ability to destabilize membranes or form complexes with DNA. PEG-b-PVBLG-8 copolymers with low (n = 76) and high (n = 287) degrees of polymerization (n) of the PVBLG-8 block were synthesized and evaluated for gene delivery. PEG-b-PVBLG-8 diblock polymers with a high degree of polymerization have a greater transfection efficiency and lower toxicity in IMR-90 cells than the commercial reagent Lipofectamine 2000. The usefulness of PEG-b-PVBLG-8 was further demonstrated via the successful transfection of hESCs without a measured loss in cell pluripotency markers.

Pearl-necklace complexes of flexible polyanions with neutral–cationic diblock copolymers

We study the complexation of very asymmetric diblock copolymers (consisting of a cationic block of 12 lysines connected to a 400 amino acid long hydrophilic polypeptide block with a net charge that is nearly zero) with oppositely charged sodium poly(acrylic acid) (NaPAA) with a range of molar masses between 2 and 1300 kg mol−1. For shorter Na-PAA chains, spherical complex coacervate micelles are formed, but for long Na-PAA chains, with molar masses in excess of 250 kg mol−1, atomic force microscopy indicates the presence of pearl-necklace structures. Complexes most likely consist of only a single NaPAA chain, complexed to multiple diblocks. Hence, the size of the complexes can be fully controlled via the NaPAA molar mass. The occurrence of pearl-necklace complexes at higher NaPAA molar masses is attributed to the packing frustration that arises due to the small size of the cationic block of the diblock copolymers.

Synthesis and photoresponsive behavior of azobenzene‐containing side‐chain liquid crystalline diblock polymers with polypeptide block

AbstractWell‐defined azobenzene‐containing side‐chain liquid crystalline diblock copolymers composed of poly[6‐(4‐methoxy‐azobenzene‐4′‐oxy) hexyl methacrylate] (PMMAZO) and poly(γ‐benzyl‐L‐glutamate) (PBLG) were synthesized by click reaction from alkyne‐ and azide‐functionalized homopolymers. The alkyne‐terminated PMMAZO homopolymers were synthesized by copper‐mediated atom transfer radical polymerization with a bromine‐containing alkyne bifunctional initiator, and the azido‐terminated PBLG homopolymers were synthesized by ring‐opening polymerization of γ‐benzyl‐L‐glutamate‐N‐carboxyanhydride in DMF at room temperature using an amine‐containing azide initiator. The thermotropic phase behavior of PMMAZO‐b‐PBLG diblock copolymers in bulk were investigated using differential scanning calorimetry and polarized light microscopy. The PMMAZO‐b‐PBLG diblock copolymers exhibited a smectic phase and a nematic phase when the weight fraction of PMMAZO block was more than 50%. Photoisomerization behavior of PMMAZO‐b‐PBLG diblock copolymers and the corresponding PMMAZO homopolymers in solid film and in solution were investigated using UV–vis. In solution, trans–cis isomerization of diblock copolymers was slower than that of the corresponding PMMAZO homopolymers. These results may provide guidelines for the design of effective photoresponsive anisotropic materials. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013

Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Rhodium Block Copolymer Complexes in Aqueous Micelles

High activity and enantioselectivity were achieved in the rhodium-catalyzed asymmetric transfer-hydrogenation reactions of ketones in pure water using a novel amphiphilic block polypeptide ligand. The covalent linkage of the catalyst to the block copolymer plays a significant role and provides higher conversions and better recyclability than regular micellar or nonmicellar systems.

Microfluidics assisted fabrication of microspheres by poly(2–hydroxyethyl methacrylate)-block-poly(l-histidine) hybrid materials and their utilization as potential drug encapsulants

A new series of synthetic polymer bioconjugate hybrid materials consisting of poly(2-hydroxyethyl meth- acrylate)(p(HEMA))as a synthetic polymer block and poly(L-histidine) (p(His)) as a polypeptide block were syn- thesized by combining atom transfer radical polymerization of HEMA with ring opening polymerization of benzyl- N-carboxy-L-histidine anhydride. The resulting biocompat- ible p(HEMA)25-b-p(His)n (n = 15, 25, 35, and 45) hybrid polymers were investigated for their use as pH-sensitive drug delivery system. Highly uniform microspheres were fabricated by using the microfluidics assisted self-assembly of these block polymers and utilized them as carriers for a chemotherapeutic agent doxorubicin and a beta-lactam antibiotic ampicillin for the evaluation of the drug-loading and release behaviors according to pH, demonstrating the release is sensitive to pH. The capability of the new p(HEMA)-b-p(His) hybrid materials to self-assemble in microenvironments and to effectively encapsulate drug molecules serves as suitable carriers for the delivery of drug molecules with varying physiochemical properties.

Self-Assembly of a Mixture System Containing Polypeptide Graft and Block Copolymers: Experimental Studies and Self-Consistent Field Theory Simulations

Self-assembly behavior of mixture systems containing poly(γ-benzyl-L-glutamate)-poly(ethylene glycol) graft (PBLG-g-PEG) and block (PBLG-b-PEG) copolymers in aqueous solution was investigated by both experiments and computer simulations. Pure graft copolymers self-assembled into vesicles, and pure block copolymers aggregated into spherical micelles or vesicles, while, for the mixture systems, hybrid cylindrical micelles were observed. In addition to the experimental observations, self-consistent field theory (SCFT) simulations were performed on the self-assembly behavior of graft/block copolymer mixtures. Simulation results reproduced the morphological transitions observed in the experiments. Moreover, from the SCFT simulations, the chain distributions of copolymers in the aggregates were obtained. For the hybrid cylindrical micelles, block copolymers were found to mainly locate at the ends of aggregates, which prevents the fusion of cylinders to vesicles. By combining experimental findings with simulation results, the mechanism regarding the morphological transition of the aggregates formed by graft/block copolymer mixtures is proposed.