Meng Huo

Redox-responsive polymers for drug delivery: from molecular design to applications

Glutathione has been regarded as a significant signal for distinguishing between tumor and normal tissue. Recently, reactive oxygen species have attracted much attention for their close connection with many diseases. Taking advantage of the physiological signals, redox-responsive polymeric drug carriers constitute a significant research area in the various stimuli-responsive polymers for biomedical applications. During the rapid development of redox-responsive polymers, molecular design and related synthetic methodology plays a crucial role. In this review, we discuss the reduction- and oxidation-responsive polymeric drug carriers from the view of functional groups, as well as their applications in controlled release.

CO2‐Responsive Nanofibrous Membranes with Switchable Oil/Water Wettability

Responsive polymer interfacial materials are ideal candidates for controlling surface wetting behavior. Here we developed smart nanostructured electrospun polymer membranes which are capable of switching oil/water wettability using CO2 as the trigger. In particular, the combination of CO2 -responsiveness and porous nanostructure enables the as-prepared membranes to be used as a novel oil/water on-off switch. We anticipate that the promising versatility and simplicity of this system would not only open up a new way of surface wettability change regulation by gas, but also have obvious advantages in terms of highly controlled oil/water separation and CO2 applications.

Electrochemical redox responsive supramolecular self-healing hydrogels based on host–guest interaction

A supramolecular hydrogel was prepared through the host–guest interaction between β-cyclodextrin (β-CD) and ferrocene (Fc) with two polymers as pendant groups. Reversible gel–sol transition was observed with the alternative stimuli of a positive potential (or an oxidant) and a negative potential (or a reductant). The hydrogel not only had good self-healing ability due to the dynamic host–guest interaction, but also was prepared under mild conditions and could respond to moderate electrochemical stimuli. Good biocompatibility endowed the hydrogel with potential practical and real-life applications, especially in tissue engineering and drug release field.

CO2-switchable drug release from magneto-polymeric nanohybrids

CO2-responsive well-defined core–shell–corona structure magnetic Fe3O4@SiO2-poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) nanocarriers have been developed as efficient drug delivery systems. The hybrid magnetic nanoparticles (MNPs) demonstrated a sandwich structure and highly super-paramagnetic biocompatibility properties as well as gas-responsive behavior. We found that the hydrodynamic radius (Rh) of the magnetic hybrid nanoparticles could be adjusted by alternate CO2/N2 treatment driving a switchable volume transition from contraction to expansion because of the CO2 responsiveness of PDMAEMA. The CO2-triggered protonation of the polymer shell gives rise to an obvious zeta potential change of the nanoparticles. Importantly, the CO2 induced reversible “on–off” transformation makes it possible to perform a dosage release of doxorubicin (DOX) in vitro in a time-controllable manner which is of great significance in controlled drug release. In the presence of CO2, the drug release rate is significantly accelerated, while low drug release could be achieved by removal of CO2 using N2. Moreover, the in vitro cytotoxicity test indicated that the CO2-responsive magnetic nanocarriers have good biocompatibility and could be safely used in living systems.

Synthesis and self-assembly of CO2-responsive dendronized triblock copolymers

Stimuli-responsive morphology evolution of polymeric self-assemblies may serve as a model to promote the understanding of cellular shape transformation. Generally, the original morphology of these self-assemblies can be obtained through delicate regulation of the ratio of hydrophobic/hydrophilic polymer chains. Regretfully, less attention has been paid to the influence of chain “thickness” on the self-assembly and stimuli-responsiveness. In this article, CO2-responsive dendronized triblock copolymers POEGMA-b-P(Gn)-b-PDEAEMA (n = 1, 2) with Frechet-type poly(aryl ether) as the dendron (Gn) were synthesized by RAFT polymerization, and the dendronized block was designed to allow the chain “thickness” tunable. We found that the generation of dendrons, the type of common solvent, and CO2-stimulus all contributed to the self-assembly of these triblock copolymers. Micelles with different sizes could be obtained in both THF/H2O and DMF/H2O, except that POEGMA-b-P(G2)-b-PDEAEMA precipitated in THF/H2O. Upon CO2 aeration, POEGMA-b-P(G1)-b-PDEAEMA micelles in THF/H2O disrupted into smaller ones while in DMF/H2O they swelled slightly. Micelles formed in DMF/H2O of POEGMA-b-P(G2)-b-PDEAEMA were much larger than that of POEGMA-b-P(G1)-b-PDEAEMA. Similarly, POEGMA-b-P(G2)-b-PDEAEMA micelles swelled to larger micelles upon CO2 triggering. Considering the tunable thickness of the dendron block, these CO2-responsive dendronized polymers may add a new dimension in biomimetic morphology transformation.

CO2-Stimulated morphology transition of ABC miktoarm star terpolymer assemblies

The integration of stimuli-responsive polymers with polymeric assemblies enables exquisite control over their nanostructures. Herein, we report the CO2-regulated self-assembly behaviors of a series of amphiphilic miktoarm star terpolymers star-[poly(ethylene glycol)-polystyrene-poly[2-(N,N-diethylamino)ethyl methacrylate]] (μ-PEG-PS-PDEA). These μ-PEG-PS-PDEA assemblies show enhanced CO2-responsibility with the increase in the molecular weight (Mn) of the PDEA segment. For μ-PEG-PS-PDEAx (x represents the Mn of the PDEA block, x = 9.3k, 12.2k, 25k), we observed an unusual sphere/vesicle-to-lamella transition upon CO2 stimulation. As the Mn of PDEA increases from 9.3k to 25k, the morphology of these lamellae evolves from nanophase segregated “E. coli-shaped” nanosheets to nanoribbons, then to nanodiscs. We studied the pH, zeta potential and the microscopy images of the assemblies before and after CO2 stimulation, and accordingly speculated the possible mechanisms for the morphology transformation and the nanophase segregation. Our results indicate that the combination of CO2 stimulation with miktoarm star polymers could potentially extend the horizon of macromolecular self-assembly.

Topological engineering of amphiphilic copolymers via RAFT dispersion copolymerization of benzyl methacrylate and 2-(perfluorooctyl)ethyl methacrylate for polymeric assemblies with tunable nanostructures

The influence of polymer topology on the nanostructure of amphiphilic copolymer assemblies has been less studied. In this contribution, we regulated the topology of the solvophobic block of poly(N,N-dimethylamino ethyl methacrylate)-b-poly(benzyl methacrylate-co-2-perfluorooctyl ethyl methacrylate) [PDMA-b-P(BzMA-co-FMA)] by reversible addition–fragmentation chain transfer (RAFT) dispersion copolymerization of BzMA and FMA at varying feed ratios. The influence of the variation in the polymer topology on the nanostructure of the corresponding assemblies was evaluated. With the increment of the FMA wt% within the solvophobic block, the size of the PDMA-b-P(BzMA-co-FMA) vesicles increases accordingly. Besides, for PDMA-b-P(BzMA-co-FMA) copolymers whose molecular weights of the solvophobic block range from 88 to 141k, by adjusting the feed ratio of BzMA/FMA, a rich variety of nanostructures were fabricated, including large compound micelles, large compound vesicles, hexagonally packed hollow hoops and nanoporous spheres. Our results indicate that topological engineering of the amphiphilic copolymers via RAFT dispersion copolymerization could be an efficient approach for regulating the nanostructure of polymer assemblies.

Semi-Fluorinated Methacrylates: A Class of Versatile Monomers for Polymerization-Induced Self-Assembly

A series of polymerization-induced self-assembly (PISA) formulations are developed based on reversible addition-fragmentation chain-transfer (RAFT) dispersion polymerization of semi-fluorinated methacrylates. Alcoholic RAFT dispersion polymerization of 2-(perfluorobutyl)ethyl methacrylate (FBEMA), 2-(perfluorohexyl)ethyl methacrylate (FHEMA), and 2-(perfluorooctyl)ethyl methacrylate (FOEMA) is systematically evaluated to extend the general usability of semi-fluorinated methacrylates to PISA. The nanostructure of the assemblies is correlated to the side-chain length of the monomer: RAFT dispersion polymerization of FBEMA produces spherical micelles, wormlike micelles, and vesicles depending on its degree of polymerization (DP), while only spheres are generated for the PISA of FHEMA. PISA of FOEMA generates liquid crystalline cylindrical micelles, whose diameter increases with the DP of FOEMA. These results demonstrate the general feasibility of semi-fluorinated methacrylates to PISA. Besides, PISA of FHEMA is also realized in a variety of solvents, including iso-propanol, toluene, dioxane, and dimethyl formamide, exhibiting the superior solvent serviceability of the PISA formulations based on semi-fluorinated methacrylates.

Polymerization-induced self-assembly of liquid crystalline ABC triblock copolymers with long solvophilic chains

Understanding the self-assembly of liquid crystalline (LC) block copolymers is challenging because of the complex influencing factors. In this article, we studied the influence of the solvophilic chain length on the self-assembly of the LC ABC triblock copolymer poly(N,N-dimethylaminoethyl methacrylate)-b-poly(benzyl methacrylate)-b-poly[2-(perfluorooctyl)ethyl methacrylate] (PDMA-b-PBzMA-b-PFOEMA) by polymerization-induced self-assembly, where PFOEMA served as the LC block. PDMA72 was used for preparing PDMA-b-PBzMA spheres with varying sizes, which were subsequently used as seeds for mediating the seeded reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of FOEMA to target PDMA-b-PBzMA-b-PFOEMA assemblies. By regulating the degree of polymerization (DP) of PBzMA and PFOEMA, a range of morphologies, including spheroids, cylinders, and spherical multicompartment micelles (MCMs), were achieved. The morphology evolution of these assemblies was further investigated by transmission electron microscopy, small angle X-ray scattering, and differential scanning calorimetry, which revealed that together with the microphase segregation of PBzMA/PFOEMA, the interchain repulsion of PDMA competes with the LC anisotropic ordering of the PFOEMA block, thus dictating the morphology of PDMA-b-PBzMA-b-PFOEMA assemblies. When the DP of PBzMA is low, LC anisotropic ordering of PFOEMA predominates, and therefore ellipsoids and cylinders are generated. When the DP of PBzMA is high enough, the microphase segregation would impair the LC anisotropic ordering of PFOEMA, hence affording spherical MCMs, where the interchain repulsion of PDMA favors a spherical shape, and the microphase segregation of PBzMA/PFOEMA results in a multicompartmental nanostructure of the micellar core. Our study thus demonstrated the influence of interchain repulsion of the solvophilic block, the microphase segregation and the LC ordering of the solvophobic blocks on the self-assembly of LC copolymers, which would be beneficial for designing LC assemblies as drug carriers and nano-actuators.

CO 2 -responsive Polymeric Fluorescent Sensor with Ultrafast Response

Abstract Response speed is one of the most important evaluation criteria for CO2 sensors. In this work, we report an ultrafast CO2 fluorescent sensor based on poly[oligo(ethylene glycol) methyl ether methacrylate]-b-poly[N,N-diethylaminoethyl methacrylate-r-4-(2-methylacryloyloxyethylamino)-7-nitro-2,1,3-benzoxadiazole] [POEGMA-b-P(DEAEMA-r-NBDMA)], in which DEAEMA units act as the CO2-responsive segment and 4-nitrobenzo-2-oxa-1,3-diazole (NBD) is the chromophore. The micelles composed of this copolymer could disassemble in 2 s upon CO2 bubbling, accompanying with enhanced fluorescence emission with bathochromic shift. Furthermore, the quantum yield of the NBD chromophore increases with both the CO2 aeration time and the NBD content. Thus we attribute the fluorescent enhancement to the inhibition of the photo-induced electron transfer between unprotonated tertiary amine groups and NBD fluorophores. The sensor is durable although it is based on “soft” materials. These micellar sensors could be facilely recycled by alternative CO2/Ar purging for at least 5 times, indicating good reversibility.