Controlled Delivery of Functionalized Gold Nanoparticles by pH-Sensitive Polymersomes

The present study reports on the development of composite gold nanoparticles (AuNPs)/polymersome formulations, based on pH-responsive biocompatible polymer vesicles integrating prefunctionalized AuNPs, doped with a hydrophobic model probe for improved multimodal drug delivery. The polymer vesicles were prepared from an amphiphilic pentablock terpolymer poly­(ε-caprolactone)-<i>b</i>-poly­(ethylene oxide)-<i>b</i>-poly­(2-vinylpyridine)-<i>b</i>-poly­(ethylene oxide)-<i>b</i>-poly­(ε-caprolactone) (PCL-PEO-P2VP-PEO-PCL), consisting of a pH-sensitive and biodegradable P2VP/PCL membrane, surrounded by neutral hydrophilic PEO looping chains. Additionally, partial quaternization of the P2VP block has been performed to introduce cationic moieties. Water-dispersible AuNPs carrying a hydrophobic molecule were encapsulated in the hydrophilic aqueous lumen of the vesicles, and the release was monitored at pH conditions simulating physiological and tumor environments. The complex delivery of the cargos from these vesicles showed improved and controlled kinetics relative to the individual nanocarriers, which could be further tuned by pH and chemical modification of the membrane forming block

Ionizable Star Copolymer-Assisted Graphene Phase Transfer between Immiscible Liquids: Organic Solvent/Water/Ionic Liquid

The present study reports on the development of a simple two-step process toward the isolation of nearly defect-free mono- and few-layer graphenes in various media. This was achieved by liquid phase pre-exfoliation of pristine graphite in the presence of an ionizable PS_<i>n</i>P2VP_<i>n</i> heteroarm star copolymer in an organic solvent and subsequent graphene shuttle between immiscible media, that is, organic solvent/water and water/ionic liquid. This polymer-assisted phase transfer of graphene sheets gave rise to enrichment of suspended nanostructures in monolayers, especially in an aqueous environment. The exfoliation efficiency was assessed through Raman and electron microscopy. Relatively high concentration suspensions of efficiently exfoliated graphene sheets of large size and in high solubilization yield, could be prepared in any kind of solvent, that is, organic low boiling point medium, aqueous environment, or ionic liquid, whereas the shuttle transfer was found to be a reversible process between organic and aqueous phases

Multiresponsive Star-Graft Quarterpolymer Monolayers

Multifunctional star-graft quarterpolymers PS_<i>n</i>[P2VP-<i>b</i>-(PAA-<i>g</i>-PNIPAM)]_<i>n</i> with two different arm types, shorter PS arms and longer P2VP-<i>b</i>-PAA block copolymer arms with grafted PNIPAM chains, were studied in terms of their ability to form micellar structures at the air/water and air/solid interfaces. Because of the pH-dependent ionization of P2VP and PAA blocks, as well as thermoresponsiveness of PNIPAM chains, these multifunctional stars have multiple responsive properties to pH, temperature, and ionic strength. We observed that the molecular surface area of the stars is the largest at basic pH, when the PAA blocks are strongly charged and extended, and PNIPAM chains are spread at the interface. At acidic conditions, the molecular surface area is the smallest because the P2VP blocks submerge into the water subphase and the PAA blocks are contracted and form hydrogen bonding with grafted PNIPAM chains. The molecular surface area of the stars at the air/water interface gradually increases at elevated temperature. We suggest that the transition across lower critical solution temperature (LCST) results in the emerging of PNIPAM chains from the water subphase to the interface due to the hydrophilic to hydrophobic transition. Moreover, at higher surface pressure, the stars tend to form intermolecular micellar aggregates above LCST. The graft density of PNIPAM chains as well as the arm number was also found to have strong effects on the thermo- and pH-response. Overall, this study demonstrates that the star block copolymer conformation and aggregation are strongly dependent on the intramolecular interactions between different blocks and spatial distribution of the arms, which can be controlled by the external conditions, including pH, temperature, ionic strength, and surface pressure

Star Polymer Unimicelles on Graphene Oxide Flakes

We report the interfacial assembly of amphiphilic heteroarm star copolymers (PS_<i>n</i>P2VP_<i>n</i> and PS_<i>n</i>(P2VP-<i>b</i>-P<i>t</i>BA)_<i>n</i> (<i>n</i> = 28 arms)) on graphene oxide flakes at the air–water interface. Adsorption, spreading, and ordering of star polymer micelles on the surface of the basal plane and edge of monolayer graphene oxide sheets were investigated on a Langmuir trough. This interface-mediated assembly resulted in micelle-decorated graphene oxide sheets with uniform spacing and organized morphology. We found that the surface activity of solvated graphene oxide sheets enables star polymer surfactants to subsequently adsorb on the presuspended graphene oxide sheets, thereby producing a bilayer complex. The positively charged heterocyclic pyridine-containing star polymers exhibited strong affinity onto the basal plane and edge of graphene oxide, leading to a well-organized and long-range ordered discrete micelle assembly. The preferred binding can be related to the increased conformational entropy due to the reduction of interarm repulsion. The extent of coverage was tuned by controlling assembly parameters such as concentration and solvent polarity. The polymer micelles on the basal plane remained incompressible under lateral compression in contrast to ones on the water surface due to strongly repulsive confined arms on the polar surface of graphene oxide and a preventive barrier in the form of the sheet edges. The densely packed biphasic tile-like morphology was evident, suggesting the high interfacial stability and mechanically stiff nature of graphene oxide sheets decorated with star polymer micelles. This noncovalent assembly represents a facile route for the control and fabrication of graphene oxide-inclusive ultrathin hybrid films applicable for layered nanocomposites

Injectable Hydrogel: Amplifying the pH Sensitivity of a Triblock Copolypeptide by Conjugating the N‑Termini via Dynamic Covalent Bonding

We explore the self-assembly behavior of aqueous solutions of an amphiphilic, pH-sensitive poly­(l-alanine)-<i>b</i>-poly­(l-glutamic acid)-<i>b</i>-poly­(l-alanine), (A₅E₁₁A₅) triblock copolypeptide, end-capped by benzaldehyde through Schiff base reaction. At elevated concentrations and under physiological pH (7.4) and ionic strength (0.15M), the bare copolypeptide aqueous solutions underwent a sol–gel transition after heating and slow cooling thermal treatment, forming opaque stiff gels due to a hierarchical self-assembly that led to the formation of β-sheet-based twisted super fibers (Popescu et al. <i>Soft Matter</i> <b>2015</b>, <i>11</i>, 331–342). The conjugation of the N-termini with benzaldehyde (Bz) through a Schiff base reaction amplifies the copolypeptide pH-sensitivity within a narrow pH window relevant for in vivo applications. Specifically, the dynamic character of the imine bond allowed coupling/decoupling of the Bz upon switching pH. The presence of Bz conjugates to the N-termini of the copolypeptide resulted in enhanced packing of the elementary superfibers into thick and short piles, which inhibited the ability of the system for gelation. However, partial cleavage of Bz upon lowering pH to 6.5 prompted recovery of the hydrogel. The sol–gel transition triggered by pH was reversible, due to the coupling/decoupling of the benzoic–imine dynamic covalent bonding, endowing thus the gelling system with injectability. Undesirably, the gelation temperature window was significantly reduced, which however can be regulated at physiological temperatures by using a suitable mixture of the bare and the Bz-conjugated coplypeptide. This triblock copolypeptide gelator was investigated as a scaffold for the encapsulation of polymersome nanocarriers, loaded with a hydrophilic model drug, calcein. The polymersome/polypeptide complex system showed prolonged probe release in pH 6.5, which is relevant to extracellular tumor environment, rendering the system potentially useful for sustained delivery of anticancer drugs locally in the tumor

Multicompartmental Microcapsules from Star Copolymer Micelles

We present the layer-by-layer (LbL) assembly of amphiphilic heteroarm pH-sensitive star-shaped polystyrene-poly­(2-pyridine) (PS_<i>n</i>P2VP_<i>n</i>) block copolymers to fabricate porous and multicompartmental microcapsules. Pyridine-containing star molecules forming a hydrophobic core/hydrophilic corona unimolecular micelle in acidic solution (pH 3) were alternately deposited with oppositely charged linear sulfonated polystyrene (PSS), yielding microcapsules with LbL shells containing hydrophobic micelles. The surface morphology and internal nanopore structure of the hollow microcapsules were comparatively investigated for shells formed from star polymers with a different numbers of arms (9 versus 22) and varied shell thickness (5, 8, and 11 bilayers). The successful integration of star unimers into the LbL shells was demonstrated by probing their buildup, surface segregation behavior, and porosity. The larger arm star copolymer (22 arms) with stretched conformation showed a higher increment in shell thickness due to the effective ionic complexation whereas a compact, uniform grainy morphology was observed regardless of the number of deposition cycles and arm numbers. Small-angle neutron scattering (SANS) revealed that microcapsules with hydrophobic domains showed different fractal properties depending upon the number of bilayers with a surface fractal morphology observed for the thinnest shells and a mass fractal morphology for the completed shells formed with the larger number of bilayers. Moreover, SANS provides support for the presence of relatively large pores (about 25 nm across) for the thinnest shells as suggested from permeability experiments. The formation of robust microcapsules with nanoporous shells composed of a hydrophilic polyelectrolyte with a densely packed hydrophobic core based on star amphiphiles represents an intriguing and novel case of compartmentalized microcapsules with an ability to simultaneously store different hydrophilic, charged, and hydrophobic components within shells

Stimuli-Responsive Amphiphilic Polyelectrolyte Heptablock Copolymer Physical Hydrogels: An Unusual pH-Response

An amphiphilic cationic polyelectrolyte based on poly­[2-(dimethylamino)­ethyl methacrylate] (polyDMA) and poly­(<i>n</i>-butyl methacrylate) (polyBuMA) with a BuMA–DMA–BuMA–DMA–BuMA–DMA–BuMA heptablock copolymer architecture was studied in aqueous media. This copolymer was found to form a physical hydrogel via the intermolecular hydrophobic association (physical cross-linking) of the BuMA blocks. The rheological properties of the heptablock hydrogels were investigated as a function of copolymer concentration, and pH. The results showed a peculiar pH-dependence of the rheological properties, remarkably different from those observed with associative telechelic polyelectrolytes. Aqueous solutions of this copolymer were free-flowing sols at low pH (below 2) and high pH (above 8), whereas they turned into gels at intermediate pH values. The rheological properties studied as a function of pH showed two additional stiff–soft–stiff gel transitions at pH 4.5 and 6.5. Small-angle neutron scattering revealed the formation of a 3D transient network of bridged flower-like micelles whose structural characteristics, i.e., micellar radius, hard-sphere radius and hard-sphere volume fraction, were smoothly evolving with the pD

Thermoresponsive Hydrogels Based on Telechelic Polyelectrolytes: From Dynamic to “Frozen” Networks

A novel thermoresponsive gelator of (B-<i>co</i>-C)-<i>b</i>-A-<i>b</i>-(B-<i>co</i>-C) topology, comprising a poly­(2-(dimethyl­amino)­ethyl methacrylate) (PDMAEMA) weak polyelectrolyte as central block, end-capped by thermosensitive poly­(triethylene glycol methyl ether methacrylate/<i>n</i>-butyl methacrylate) [P­(TEGMA-<i>co</i>-<i>n</i>BuMA)] random copolymers, was designed and explored in aqueous media. The main target of this design was to control the dynamics of the stickers by temperature as to create an injectable hydrogel that behaves as a weak gel at low temperature and as a strong gel at physiological temperature. Indeed, at low temperatures, the system behaves like a viscoelastic complex fluid (dynamic network), while at higher temperatures, an elastic hydrogel is formed (“frozen” network). The viscosity increases exponentially upon heating, about 5 orders of magnitude from 5 to 45 °C, which is attributed to the exponential increase of the lifetime of the self-assembled stickers. The integration of thermo- and shear responsive properties in the gelator endows the gel with injectability. Moreover, the gel can be rapidly recovered upon cessation of the applied stress at 37 °C, simulating conditions similar to those of injection through a 28-gauge syringe needle. All these hydrogel properties render it a good candidate for potential applications in cell transplantation through injection strategies