Unimer Micelles Research Articles

Elucidation of Protonation Cooperativity of a STING-Activating Polymer.

Stimuli-responsive nanomaterials have the potential to improve the performance and overcome existing barriers of conventional nanotherapeutics. Molecular cooperativity design in stimuli-responsive nanomedicine can amplify physiological signals, enabling a cooperative response for improved diagnostic and therapeutic precision. Previously, this work reported an ultra-pH-sensitive polymer, PEG-b-PC7A, that possesses innate immune activating properties by binding to the stimulator of interferon genes (STING) through polyvalent phase condensation. This interaction enhances STING activation and synergizes with the endogenous STING ligand for robust cancer immunotherapy. Despite its successes in innate immune activation, the fundamental physicochemical and pH-responsive properties of PC7A require further investigation. Here, this study elucidates the protonation cooperativity driven by the phase transition of PC7A copolymer. The highly cooperative system displays an "all-or-nothing" proton distribution between highly charged unimer (all) and neutral micelle (nothing) states without gradually protonated intermediates. The binary protonation behavior is further illustrated in pH-precision-controlled release of a representative anticancer drug, β-lapachone, by PC7A micelles over a noncooperative PE5A polymer. Furthermore, the bimodal distribution of protons is represented by a high Hill coefficient (nH >9), featuring strong positive cooperativity. This study highlights the nanoscale pH cooperativity of an immune activating polymer, providing insights into the physicochemical characterization and design parameters for future nanotherapeutics development.

Amphiphilic Fluorinated Unimer Micelles as Nanocarriers of Fluorescent Probes for Bioimaging.

The unique self-assembly properties of unimer micelles are exploited for the preparation of fluorescent nanocarriers embedding hydrophobic fluorophores. Unimer micelles are constituted by a (meth)acrylate copolymer with oligoethyleneglycol and perflurohexylethyl side chains (PEGMA90-co-FA10) in which the hydrophilic and hydrophobic comonomers are statistically distributed along the polymeric backbone. Thanks to hydrophobic interactions in water, the amphiphilic copolymer forms small nanoparticles (<10 nm), with tunable properties and functionality. An easy procedure for the encapsulation of a small hydrophobic molecule (C153 fluorophore) within unimer micelles is presented. UV-vis, fluorescence, and fluorescence anisotropy spectroscopic experimental data demonstrate that the fluorophore is effectively embedded in the nanocarriers. Moreover, the nanocarrier positively contributes to preserve the good emissive properties of the fluorophore in water. The efficacy of the dye-loaded nanocarrier as a fluorescent probe is tested in two-photon imaging of thick ex vivo porcine scleral tissue.

Thermoresponsive Reversible Unimer Micelles of Amphiphilic Fluorinated Copolymers

AbstractAmphiphilic fluorinated copolymers PEGMAx‐co‐FAy and TEGMAx‐co‐FAy are prepared by activators regenerated by electron transfer atom transfer radical polymerization (ARGET‐ATRP). All polymers present a reversible thermoresponsive lower critical solution temperature‐type behavior, and a cloud point temperature (Tc) in the range of 30–60 °C strictly dependent on the length of the oxyethylene side chain, the content of the hydrophobic counits, and the concentration of the solution. Combined small angle X‐ray scattering (SAXS) and dynamic light scattering measurements are used to study the self‐assembly behavior in water, organic solvents (tetrahydrofuran [THF] and dimethylformamide [DMF]), and a fluorinated solvent (hexafluorobenzene [HFB]). SAXS confirms the formation of compact‐globular single‐chain self‐folded unimer micelles in water below Tc, which generally presents small hydrodynamic diameters (Dh ≤ 8 nm) as a result of the folding of the hydrophobic perfluorohexylethyl acrylate counits. The copolymers are also able to form reverse unimer micelle in HFB. The copolymers are not able to self‐assemble in unimer micelles in THF or DMF solutions, in which they adopt conventional random coil conformations.

Self-Assembled Amphiphilic Fluorinated Random Copolymers for the Encapsulation and Release of the Hydrophobic Combretastatin A-4 Drug.

Water-soluble amphiphilic random copolymers composed of tri(ethylene glycol) methacrylate (TEGMA) or poly(ethylene glycol) methyl ether methacrylate (PEGMA) and perfluorohexylethyl acrylate (FA) were synthesized by ARGET-ATRP, and their self-assembling and thermoresponsive behavior in water was studied by dynamic light scattering (DLS) and UV-vis spectroscopy. The copolymer ability to self-fold in single-chain nano-sized structures (unimer micelles) in aqueous solutions was exploited to encapsulate Combretastatin A-4 (CA-4), which is a very hydrophobic anticancer drug. The cloud point temperature (Tcp) was found to linearly decrease with increasing drug concentration in the drug/copolymer system. Moreover, while CA-4 was preferentially incorporated into the unimer micelles of TEGMA-ran-FA, the drug was found to induce multi-chain, submicro-sized aggregation of PEGMA-ran-FA. Anyway, the encapsulation efficiency was very high (≥81%) for both copolymers. The drug release was evaluated in PBS aqueous solutions both below and above Tcp for TEGMA-ran-FA copolymer and below Tcp, but at two different drug loadings, for PEGMA-ran-FA copolymer. In any case, the release kinetics presented similar profiles, characterized by linear trends up to ≈10–13 h and ≈7 h for TEGMA-ran-FA and PEGMA-ran-FA, respectively. Then, the release rate decreased, reaching a plateau. The release from TEGMA-ran-FA was moderately faster above Tcp than below Tcp, suggesting that copolymer thermoresponsiveness increased the release rate, which occurred anyway by diffusion below Tcp. Cytotoxicity tests were carried out on copolymer solutions in a wide concentration range (5–60 mg/mL) at 37 °C by using Balb/3T3 clone A31 cells. Interestingly, it was found that the concentration-dependent micro-sized aggregation of the amphiphilic random copolymers above Tcp caused a sort of “cellular asphyxiation” with a loss of cell viability clearly visible for TEGMA-ran-FA solutions (Tcp below 37 °C) with higher copolymer concentrations. On the other hand, cells in contact with the analogous PEGMA-ran-FA (Tcp above 37 °C) presented a very good viability (≥75%) with respect to the control at any given concentration.

PH-Responsive Association Behavior of Biocompatible Random Copolymers Containing Pendent Phosphorylcholine and Fatty Acid.

Well-defined pH-responsive biocompatible random copolymers composed of 2-(methacryloyloxy)ethyl phosphorylcholine and varying quantities of sodium 11-(acrylamido)undecanoate (AaU) (fAaU = 0-58 mol %) were synthesized via reversible addition-fragmentation chain transfer radical polymerization. The pH-responsive association and dissociation behavior of the random copolymers was studied via turbidity, 1H nuclear magnetic resonance relaxation time, dynamic light scattering, static light scattering (SLS), and fluorescence measurements. At basic pH levels, the random copolymers dissolved in water in a unimer state because the AaU units behaved in a hydrophilic manner as a result of the ionization of the pendent fatty acids. The random copolymers with fAaU < 52 mol % associated intramolecularly within a single polymer chain to form unimer micelles at pH 3 because of the protonation of the pendent fatty acids. On the other hand, the random copolymer with fAaU ≥ 52 mol % formed intermolecular aggregates composed of four polymer chains at pH 3, as established by the SLS measurements. The random copolymers displayed the ability to solubilize hydrophobic guest molecules, such as N-phenyl-1-naphthylamine, into the hydrophobic microdomain formed by the pendent dehydrated fatty acids at acidic pHs. At pH 4, 1-pyrememethanol is captured by the random copolymer with fAaU = 52 mol %, and it is released from the random copolymer above pH 9. Furthermore, the mucoadhesive properties of the random copolymer with fAaU = 9 mol % were studied using a surface plasmon resonance technique. The copolymer was adsorbed onto mucin at pH 3; however, the adsorption decreased at pH 7.4.

Using High Molecular Precision to Study Enzymatically Induced Disassembly of Polymeric Nanocarriers: Direct Enzymatic Activation or Equilibrium-Based Degradation?

Enzyme-responsive polymers and their assemblies offer great potential to serve as key materials for the design of drug delivery systems and other biomedical applications. However, the utilization of enzymes to trigger the disassembly of polymeric amphiphiles, such as micelles, also suffers from the limited accessibility of the enzyme to moieties that are hidden inside the assembled structures. In this Perspective, we will discuss examples for the utilization of high molecular precision that dendritic structures offer to study the enzymatic degradation of polymeric amphiphiles with high resolution. Up to date, several different amphiphilic systems based on dendritic blocks have all shown that small changes in the hydrophobicity and amphiphilicity strongly affected the degree and rate of enzymatic degradation. The ability to observe the huge effects due to relatively small variations in the molecular structure of polymers can explain the limited enzymatic degradation that is often observed for many reported polymeric assemblies. The observed trends imply that the enzymes cannot reach the hydrophobic core of the micelles, and instead, they gain access to the amphiphiles by the unimer–micelle equilibrium, making the unimer exchange rate a key parameter in tuning the enzymatic degradation rate. Several approaches that are aimed at overcoming the stability–responsiveness challenge are discussed as they open the way to the design of stable and yet enzymatically responsive polymeric nanocarriers.

Morphology transition of amphiphilic homopolymer self-assemblies in water triggered by pendant design and chain length

In this paper, we examined self-assembly of amphiphilic homopolymers bearing the double brush side chains of a hydrophilic PEG and various hydrophobic units including butyl, octyl, dodecyl, octadecyl, and oleyl groups in water. Analyzed by size exclusion chromatography coupled with multiangle laser light scattering, those homopolymers formed uniform micelles, unimer micelles, and large aggregates like rod micelles in water; the morphology depended on the hydrophobic side chains and changed at a certain threshold degree of polymerization (DPth). The homopolymer comprising butyl groups folded into compact micelles via intramolecular association in water, independent of molecular weight. In contrast, the homopolymer carrying octyl groups formed either uniform micelles via multichain association (<DPth) or unimer micelles via single chain folding (>DPth). The homopolymers carrying dodecyl, octadecyl, and oleyl groups exclusively undergo multichain association in water but form either uniform micelles (<DPth) or large aggregates (>DPth). Uniquely, those DPth values decreased with increasing the hydrophobicity of the pendants; more hydrophobic homopolymers tend to form large aggregates at shorter polymer chains. Additionally, those homopolymers with broad molecular weight distribution induced chain length-dependent self-sorting to simultaneously produce uniform micelles and large aggregates in water.

Selective Coupling and Polymerization of Folded Polymer Micelles to Nanodomain Self-Assemblies.

Herein, we developed selective coupling and polymerization systems of folded polymer micelles via physical interaction in water. The polymer micelles serve as nanodomains to provide double core micelles, alternating necklace micelles, and micelle-connected hydrogels. For this, cation- or anion-tail unimer micelles and amine- or carboxy-tail unimer micelles were designed; the unimer micelles consist of folded amphiphilic random copolymers carrying hydrophilic poly(ethylene glycol) and hydrophobic or hydrogen-bonding pendants. Mixing a cation-tail micelle and an anion-tail micelle, and even the combination of a double cation-tail micelle and a double anion-tail micelle, selectively provided double-core micelles in water without forming large aggregates. Double core micelles afforded structural transformation into linear or cyclic polymers and dynamic exchange of the micelle domains. In contrast, mixing amine-tail micelles and carboxy-tail micelles gave an alternating necklace micelle or a hydrogel. The controlled connection of polymer micelles was achieved by designing suitable physical interaction. This technique opened new ways to create various nanodomain self-assemblies with controlled higher-order structure.

Controlled Self-Assembly of Amphiphilic Random Copolymers into Folded Micelles and Nanostructure Materials.

In this review, we report controlled self-assembly systems of amphiphilic random copolymers in aqueous or organic media and the solid state to produce folded micelles, related nanoaggregates, vesicles, and microphase separation materials. The key features of random copolymer self-assemblies are 1) self-folding of polymer chains, 2) precision self-assembly of side chains, and 3) dynamic self-sorting and selective recognition. Typically, random copolymers bearing hydrophilic poly(ethylene glycol) and hydrophobic alkyl groups folded into small unimer micelles (~10 nm) via the association of the hydrophobic groups in water. Importantly, those random copolymers afforded precision intermolecular self-assembly into multichain micelles; the size, aggregation number, and thermoresponsive properties can be controlled as desired by tuning their molecular weight, composition, and side chains. The binary mixture of different random copolymers further self-sorted via chain exchange in water to simultaneously form discrete micelles. Namely, amphiphilic random copolymers can dynamically recognize themselves in complex media like natural biomolecules and proteins. Amphiphilic random copolymers opened new ways to create self-assembled materials with well-defined nanostructures and compartments, dynamic recognition properties, and functions.

Relationships between Diffusion and Viscoelasticity of Associative Polymer Networks

Hydrophobically ethoxylated modified urethane (HEUR) form the flower micelles and transient network structures through the aggregation of end groups depending on the polymer concentration. The HEUR networks show the viscoelastic relaxation which is described by the Maxwell model. Although there have been many attempts to understand and predict the molecular mechanism, the full understanding remains incomplete. To understand the relaxation mechanism of associative polymers, we measured the linear viscoelasticity and the diffusibility using the fluorescence recovery after photobleaching method. With increasing the polymer concentration, the self-diffusion coefficient decreased, while the relaxation time increased, suggesting that the viscoelastic relaxation is correlated with the diffusion of the polymers. The calculated diffusion distance of the HEUR chains within the viscoelastic relaxation time is 100 times larger than the size of a HEUR chain. This significant deviation suggests that some of the HEUR chains diffuse quickly through the unimer and flower micelles at low concentrations and through the recombination process of the network strands at high concentrations.

Orthogonal Folding of Amphiphilic/Fluorous Random Block Copolymers for Double and Multicompartment Micelles in Water.

Here, we report orthogonal folding and self-assembly systems of amphiphilic/fluorous random block copolymers for double core and multicompartment micelles in water. For this, we developed the precision folding techniques of polymer chains via the selective self-assembly of the pendant groups. Typically, A/C-B/C random block copolymers were designed: Hydrophobic dodecyl groups (A) and fluorous fluorinated octyl groups (B) were introduced into the respective blocks, while hydrophilic poly(ethylene glycol) chains (C) were randomly incorporated into all the segments. By controlling the chain length and composition of the respective blocks, the copolymers induce orthogonal single-chain folding in water to form double-compartment micelles comprising hydrophobic and fluorous cores. The copolymers were site-selectively folded in a fluoroalcohol to result in tadpole unimer micelles comprising a hydrophobic A/C unimer micelle and an unfolded fluorous B/C chain. Additionally, asymmetric A/C-B/C random block copolymers with short and highly hydrophobic or fluorous segments were effective for multicompartment micelles in water.

Self‐assembly of amphiphilic ABA random triblock copolymers in water

ABSTRACTSelf‐assembly of amphiphilic ABA random triblock copolymers in water serves as a novel approach to create unique structure micelles connected with flexible linkages. The ABA triblock copolymers consist of amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) and hydrophobic dodecyl pendants as the A segments and a hydrophilic poly(ethylene oxide) (PEO) as the middle B segment. The A block is varied in dodecyl methacrylate content of 20%–50% and degree of polymerization (DP) of 100‐200. By controlling the composition and DP of the A block, various architectures can be tailor‐made as micelles in water: PEO‐linked double core unimer micelles, PEO‐looped unimer or dimer micelles, and multichain micelles. Those PEO‐linked or looped micelles further exhibit thermoresponsive solubility in water. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 313–321

Intramolecular Folding or Intermolecular Self-Assembly of Amphiphilic Random Copolymers: On-Demand Control by Pendant Design

Amphiphilic random copolymers comprising different hydrophilic poly(ethylene glycol) (PEG, average number of oxyethylene units = 4.5 or 8.5) and hydrophobic butyl or dodecyl pendants were designed to investigate self-folding and self-assembly behavior in water. The copolymers with controlled composition and chain length were synthesized by ruthenium-catalyzed living radical copolymerization. We revealed that the pendant design was one of the most critical factors to selectively induce intramolecular self-folding or intermolecular self-assembly. In the case of 30 mol % hydrophobic monomers, random copolymers bearing short PEG (on average 4.5 oxyethylene units) and butyl pendants intramolecularly self-folded into unimer micelles in water, independent of chain length. The size of unimer micelles thus increased with increasing chain length. In contrast, random copolymers bearing long dodecyl pendants intermolecularly self-assembled into uniform multichain micelles; the size depended on composition and PEG len...

The Temperature‐Responsive Nanoassemblies of Amphiphilic Random Copolymers Carrying Poly(siloxane) and Poly(oxyethylene) Pendant Chains

AbstractNovel amphiphilic random copolymers carrying poly(oxyethylene) and poly(siloxane) pendant chains are synthesized by atom transfer radical polymerization starting from either a fluorescent, julolidine‐based initiator, or a nonfluorescent initiator. For both copolymer systems, dynamic light scattering measurements carried out on aqueous solutions as a function of temperature reveal the occurrence of a sharp and fully reversible transition between two different self‐associative states of individual, single‐chain self‐folded nanoassemblies, so‐called unimer micelles, (Dh = 8–10 nm) and collapsed multichain aggregates (Dh = 700–1400 nm) at a critical temperature Tc. Covalently linked julolidine terminal and added ethidium bromide are separately used as fluorescent probes and both prove the temperature‐dependence of the different self‐association of the copolymers in water.

The self‐assembly over nano‐ to submicro‐length scales in water of a fluorescent julolidine‐labeled amphiphilic random terpolymer

ABSTRACTA novel fluorescent‐labeled amphiphilic random terpolymer is synthesized by controlled radical polymerization of a fluorescent molecular rotor monomer, 2‐cyano‐2‐[4‐vinyl(1,1′‐biphenyl)‐4′‐yl]vinyljulolidine, a hydrophilic monomer, poly (ethylene glycol) methyl ether methacrylate, and a hydrophobic monomer, perfluorohexylethyl acrylate. Combined dynamic light scattering and fluorescence emission spectroscopy measurements are used to investigate its self‐assembly in water solution. Self‐assembled nanostructures with a hydrodynamic diameter size Dh of 4 ± 1 nm are detected due to the single‐chain folding of the terpolymer in unimer micelles. The fluorescence emission intensity of the terpolymer in water solution is found to be one order of magnitude higher than that in organic solvents, as a result of the preferential encapsulation of the julolidine co‐units in hydrophobic compartments of the unimer micelles. The temperature dependence of the self‐associative behavior of the amphiphilic terpolymer is also investigated and a critical temperature is identified at which a transition between single‐chain unimer micelles and multi‐chain aggregates (Dh = 400 ± 40 nm) reversibly takes place on heating–cooling cycles. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 797–804

Self‐Assembly of Amphiphilic Random Copolyacrylamides into Uniform and Necklace Micelles in Water

Amphiphilic random copolyacrylamides bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl pendants induce precision self‐assembly to produce quite small uniform and/or necklace micelles (≈10 nm) in water. The size, structure, and thermoresponsive properties of the micelles are controlled by the primary structure (composition and chain length) of the copolymers. For this, random copolymers with different composition, chain length, and molecular weight distribution are synthesized by iron‐catalyzed living or free radical copolymerization of PEG acrylamide and dodecyl acrylamide (DAAm). The copolymers with controlled molecular weight (degree of polymerization: ≈40) intermolecularly self‐assemble and/or self‐fold to form uniform (multichain or unimer) micelles in water; the size increases with increasing hydrophobic DAAm content (19–57 mol%: Mw = 43 900–191 000). In contrast, random copolymers with relatively small DAAm content (&lt;35 mol%) and broad molecular weight distribution provide both uniform and necklace micelles in water.

Backbone Degradable N-(2-Hydroxypropyl)methacrylamide Copolymer Conjugates with Gemcitabine and Paclitaxel: Impact of Molecular Weight on Activity toward Human Ovarian Carcinoma Xenografts.

Degradable diblock and multiblock (tetrablock and hexablock) N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-gemcitabine (GEM) and -paclitaxel (PTX) conjugates were synthesized by reversible addition-fragmentation chain-transter (RAFT) copolymerization followed by click reaction for preclinical investigation. The aim was to validate the hypothesis that long-circulating conjugates are needed to generate a sustained concentration gradient between vasculature and a solid tumor and result in significant anticancer effect. To evaluate the impact of molecular weight of the conjugates on treatment efficacy, diblock, tetrablock, and hexablock GEM and PTX conjugates were administered intravenously to nude mice bearing A2780 human ovarian xenografts. For GEM conjugates, triple doses with dosage 5 mg/kg were given on days 0, 7, and 14 (q7dx3), whereas a single dose regime with 20 mg/kg was applied on day 0 for PTX conjugates treatment. The most effective conjugates for each monotherapy were the diblock ones, 2P-GEM and 2P-PTX (Mw ≈ 100 kDa). Increasing the Mw to 200 or 300 kDa resulted in decrease of activity most probably due to changes in the conformation of the macromolecule because of interaction of hydrophobic residues at side chain termini and formation of "unimer micelles". In addition to monotherapy, a sequential combination treatment of diblock PTX conjugate followed by GEM conjugate (2P-PTX/2P-GEM) was also performed, which showed the best tumor growth inhibition due to synergistic effect: complete remission was achieved after the first treatment cycle. However, because of low dose applied, tumor recurrence was observed 2 weeks after cease of treatment. To assess optimal route of administration, intraperitoneal (i.p.) application of 2P-GEM, 2P-PTX, and their combination was examined. The fact that the highest anticancer efficiency was achieved with diblock conjugates that can be synthesized in one scalable step bodes well for the translation into clinics.

Molecular basis of cooperativity in pH-triggered supramolecular self-assembly.

Supramolecular self-assembly offers a powerful strategy to produce high-performance, stimuli-responsive nanomaterials. However, lack of molecular understanding of stimulated responses frequently hampers our ability to rationally design nanomaterials with sharp responses. Here we elucidated the molecular pathway of pH-triggered supramolecular self-assembly of a series of ultra-pH sensitive (UPS) block copolymers. Hydrophobic micellization drove divergent proton distribution in either highly protonated unimer or neutral micelle states along the majority of the titration coordinate unlike conventional small molecular or polymeric bases. This all-or-nothing two-state solution is a hallmark of positive cooperativity. Integrated modelling and experimental validation yielded a Hill coefficient of 51 in pH cooperativity for a representative UPS block copolymer, by far the largest reported in the literature. These data suggest hydrophobic micellization and resulting positive cooperativity offer a versatile strategy to convert responsive nanomaterials into binary on/off switchable systems for chemical and biological sensing, as demonstrated in an additional anion sensing model.

Amphiphilic Random Copolymers with Hydrophobic/Hydrogen-Bonding Urea Pendants: Self-Folding Polymers in Aqueous and Organic Media

Urea and poly(ethylene glycol) (PEG)-functionalized amphiphilic random copolymers served as self-folding polymers in both water and chloroform via hydrophobic and/or hydrogen-bonding interactions. For this, a urea-bearing methacrylate (BPUMA) was newly designed as a trigger monomer. Various random, gradient, and block copolymers were synthesized by living radical copolymerization of PEG methyl ether methacrylate (PEGMA) and BPUMA to systematically survey folding/association properties. Importantly, self-folding in both water and chloroform requires the random incorporation of BPUMA along a chain and the control of its composition, while gradient or block counterparts tend to induce multichain aggregation. Typically, 30–40 mol % BPUMA random copolymers effectively fold in water to form compact globular unimer micelles with hydrophobic/hydrogen-bonding core covered by multiple PEG arm chains. The dual functionalization of polymers with hydrophilic PEG and hydrophobic/hydrogen-bonding urea units afforded sin...

Formation of Polyion Complex (PIC) Micelles and Vesicles with Anionic pH-Responsive Unimer Micelles and Cationic Diblock Copolymers in Water.

A random copolymer (p(A/MaU)) of sodium 2-(acrylamido)-2-methylpropanesulfonate (AMPS) and sodium 11-methacrylamidoundecanate (MaU) was prepared via conventional radical polymerization, which formed a unimer micelle under acidic conditions due to intramolecular hydrophobic interactions between the pendant undecanoic acid groups. Under basic conditions, unimer micelles were opened up to an expanded chain conformation by electrostatic repulsion between the pendant sulfonate and undecanoate anions. A cationic diblock copolymer (P163M99) consisting of poly(3-(methacrylamido)propyl)trimethylammonium chloride (PMAPTAC) and hydrophilic polybetaine, 2-(methacryloyloxy)ethylphosphorylcholine (MPC), blocks was prepared via controlled radical polymerization. Mixing of p(A/MaU) and P163M99 in 0.1 M aqueous NaCl under acidic conditions resulted in the formation of spherical polyion complex (PIC) micelles and vesicles, depending on polymer concentration before mixing. Shapes of the PIC micelles and vesicles changed under basic conditions due to collapse of the charge balance between p(A/MaU) and P163M99. The PIC vesicles can incorporate nonionic hydrophilic guest molecules, and the PIC micelles and vesicles can accept hydrophobic guest molecules in the hydrophobic core formed from p(A/MaU).