Redox-responsive Properties Research Articles

Poly(aspartic acid) hydrogels showing reversible volume change upon redox stimulus

Redox and pH responsive hydrogels were synthesized, which can serve as matrices for smart drug delivery systems exploiting the redox and pH gradients in the human body. Water soluble thiolated poly(aspartic acid), a biocompatible synthetic polymer, enables us to cross-link in water with a non-cleavable cross-linker, poly(ethylene glycol) diglycidyl ether. The permanent cross-linker establishes stable polymer hydrogels regardless of the redox environment, thus the gels swell but do not dissolve upon redox stimuli. The reversible response upon redox stimulus was induced by thiol-disulphide transformation inside the hydrogel. The degree of swelling and the stiffness of the macroscopic hydrogels were controlled by their chemical composition including thiol content and cross-linking ratio as well as the redox state of the hydrogels. The degree of swelling of the hydrogels showed strong pH dependence due to the polyelectrolyte nature of the polymer network. Release of a macromolecular model drug was considerably faster in reducing than in oxidising environment, which indicates the potential use of the synthesized hydrogels as redox responsive drug delivery systems. Nanogels were prepared in water-in-oil emulsion and displayed redox-responsive properties. The hydrodynamic diameter of the nanogels strongly increased upon the cleavage of the disulphide linkages in reducing solution without the disruption of the gels.

Selenium-Doped Carbon Quantum Dots for Free-Radical Scavenging.

Heteroatom doping is an effective way to adjust the fluorescent properties of carbon quantum dots. However, selenium-doped carbon dots have rarely been reported, even though selenium has unique chemical properties such as redox-responsive properties owing to its special electronegativity. Herein, a facile and high-output strategy to fabricate selenium-doped carbon quantum dots (Se-CQDs) with green fluorescence (quantum yield 7.6 %) is developed through the hydrothermal treatment of selenocystine under mild conditions. Selenium heteroatoms endow the Se-CQDs with redox-dependent reversible fluorescence. Furthermore, free radicals such as . OH can be effectively scavenged by the Se-CQDs. Once Se-CQDs are internalized into cells, harmful high levels of reactive oxygen species (ROS) in the cells are decreased. This property makes the Se-CQDs capable of protecting biosystems from oxidative stress.

Synthesis of amphiphilic block copolymers containing ferrocene–boronic acid and their micellization, redox-responsive properties and glucose sensing

The authors wish to correct the following mistakes and unclear description in their publication.

Triple stimuli-responsive supramolecular assemblies based on host-guest inclusion complexation between β-cyclodextrin and azobenzene

The host polymer β-cyclodextrin-poly[(2-(2-methoxyethoxy)ethylmethacrylate)-co-oligo(ethylene glycol) methacrylate] [β-CD-P(MEO2MA-co-OEGMA)] was prepared by click chemistry and atom transfer radical polymerization (ATRP), and the guest polymer poly(ε-caprolactone)-SS-poly(ethylene glycol) with azobenzene (Azo) group at one end (Azo-PCL-SS-PEG) was synthesized by the combination of ring-opening polymerization (ROP) and esterification reaction. Based on the inclusion complexation between β-CD and Azo groups, the supramolecular polymer β-CD-P(MEO2MA-co-OEGMA)/Azo-PCL-SS-PEG was successfully obtained. Benefitting from the amphiphilicity, the supramolecular polymer could self-assemble into spherical micelles in aqueous solution, and the supramolecular micelles presented obvious UV light-, thermo- and redox-responsive properties. Alternating irradiation of the solution with UV or visible light could induce the reversible supramolecular self-assembly and disassembly of the micelles. When the temperature of the solution increased above the lower critical solution temperature (LCST) of P(MEO2MA-co-OEGMA) chains, the micelles became smaller and aggregated with each other. Moreover, after adding DTT into the micellar solution, the spherical micelles changed into irregular aggregates.

End-Capping Strategies for Triggering End-to-End Depolymerization of Polyglyoxylates

Polymers that undergo end-to-end depolymerization in response to the cleavage of a stimuli-responsive end-cap are promising for diverse applications from drug delivery to responsive coatings and plastics. It is critical that the end-cap is designed to respond to an appropriate stimulus for the application. In the current work, end-caps for triggering the depolymerization of poly(ethyl glyoxylate) (PEtG) were explored. First, a phenylboronate, a disulfide, and an azobenzene were utilized to impart redox-responsive properties to PEtG. Then, methoxy-substituted trityl groups were used to provide sensitivity to mild acid. A multiresponsive platform was also introduced, allowing PEtG to respond to multiple stimuli, either simultaneously or independently. Incorporation of a cross-linkable trialkene end-cap enabled the preparation of networks that could subsequently be depolymerized. Finally, high molar mass PEtG could be depolymerized by mechanical stimulation independent of the end-cap. It is anticipated that ...

Thermal and redox dual responsive poly(L-glutamate) with oligo(ethylene glycol) side-chains

A series of poly(L-glutamate)s grafted with oligo(ethylene glycol) (OEG) side-chains through the thioether linkages (PALG n -g-EG x , x = 2, 3 and 4) were prepared by ring-opening polymerization (ROP) of γ-allyl-L-glutamate N-carboxyanhydride (ALG-NCA) and thiol-ene photoaddition. The chemical structures and physical properties were characterized by 1H-NMR, Fourier transform infrared (FTIR), circular dichroism (CD), etc. The PALG n -g-EG x samples with x = 3 and 4 displayed lower critical solution temperature (LCST) in water due to the presence of OEG units. The clouding point (CP) of polypeptides can be finely tuned by changing the side chain structures, molecular weights and sample concentrations. In addition, the thioether linkages in the side chains offer additional redox-responsive properties. The influence of both OEG units and thioether linkages on the LCST behavior was systematically investigated. This work provides an efficient way to prepare multi-stimuli responsive materials with highly tunable properties.

Fabrication of autofluorescent porous silica nanoparticles for redox-responsive drug release

Porous silica nanoparticles were prepared by emulsion-condensation route. The silica nanoparticles with diameter of 50nm have both accessible center-radial large pore channels (19.9nm) and small pore size of 3.5nm. The hierarchical porous structure endows them large pore volume for loading drugs and sustained release property. The silica nanoparticles were further modified with glucose-oxidized glutathione. The formulated Schiff base and disulfide bonds render the silica nanoparticles auto-fluorescent and redox-responsive properties. The cleavage of disulfide bonds caused by reactive thiols facilitates aminomethylbenzoic acid (AMA) release. The release of drug leads to the loss of fluorescence, which would be used to monitor the drug delivery and carrier distribution.

CD44-specific nanoparticles for redox-triggered reactive oxygen species production and doxorubicin release

CD44-specific and redox-responsive nanoparticles were prepared by coating a bioreducible chitosan-based nanoparticles with hyaluronic acid for intracellular glutathione-triggered reactive oxygen species (ROS) production and doxorubicin (DOX) release. Chitosan (CS) was conjugated with a copper chelator, D-penicillamine (D-pen), to obtain a CS-SS-D-pen conjugate through the formation of a disulfide bond. D-pen release from the conjugate was triggered by intracellular glutathione (GSH) via reducing biologically reversible disulfide bonds. Self-assembled CS-SS-D-pen nanoparticles were prepared through ionotropic gelation with tripolyphosphate and subsequently coated with hyaluronic acid (HA). The HA-coated CS-SS-D-pen NPs were reduced by GSH to release free D-pen and trigger ROS production via a series of reactions involving Cu(II)-catalyzed D-pen oxidation and H2O2 generation. DOX was loaded into the HA-coated CS-SS-D-pen NPs by a method involving the complexation of DOX with Cu(II) ions. The Cu(II)–DOX complex-loaded NPs exhibited redox-responsive release properties which accelerated DOX release at a higher glutathione level (10mM). Confocal fluorescence microscopy demonstrated that the Cu(II)–DOX-loaded NPs effectively delivered DOX to human colon adenocarcinoma cells (HT-29) by active targeting via HA–CD44 interactions. Intracellular ROS generated from the HA-coated CS-SS-D-pen NPs sensitized cancer cells to DOX-induced cytotoxicity. In vitro cytotoxicity assays revealed that Cu(II)–DOX-loaded NPs sensitized cells to DOX-induced cytotoxicity in CD44-overexpressing HT-29 cells compared to CD44 low-expressing HCT-15 cells. Statement of SignificanceIn this manuscript, we develop a CD44-targetable loaded with nanoparticles Cu(II)–DOX complex. The nanoparticles exhibited redox-responsive properties, which triggered reactive oxygen species (ROS) production and accelerated DOX release. The Cu(II)–DOX-loaded nanoparticle sensitized cells to DOX-induced cytotoxicity in CD44-overexpressing HT-29 cells.To our knowledge, this is the first report showing the combination of CD44-targeting and redox-responsive property for triggering ROS production and subsequent drug release. We believe our findings would appeal to the readership of Acta Biomaterialia because the study bring new and interesting ideals in the development of specific and stimuli-responsive nanoparticles as drug carrier for cancer therapy.

Biodegradable thermal- and redox-responsive poly(l-glutamate) with Y-shaped oligo(ethylene glycol) side-chain and tunable phase transition temperature

A series of poly(l-glutamate) bearing Y-shaped oligo(ethylene glycol)x side-chains were synthesized via a combination of ROP and thiol–yne photoaddition. The polypeptides showed dual thermal and redox-responsive properties.

Ionic self-assembled fluorescent microfibres with electrochemical properties

The fluorescent microfibres with redox-responsive properties were prepared via the ionic self-assembly route from complexes of redox-responsive N,N-dimethylferrocenylmethylhexadecylammonium bromide and methyl orange dye molecule. The length of microfibres is from tens of micrometres to almost a millimetre and the width is about 500 mm to 2 μm. Steady state fluorescence spectroscopy shows strong fluorescent properties of the supramolecular self-assembled microfibres, which may have potential applications in electro-photo molecular switching device.

Dual Temperature and Thiol‐Responsive POEOMA‐Multisegmented Polydisulfides: Synthesis and Thermoresponsive Properties

New thermoresponsive polydisulfides of POEOMA multiblocks linked with disulfide bonds having redox-responsive properties are reported. These POEOMA-multisegmented polydisulfides were synthesized by a new method employing a combined RAFT/aminolysis and reversible thiol-disulfide redox reaction that centers on the synthesis of new disulfide-labeled difunctional RAFT agent. RAFT polymerization proceeded in living fashion, yielding well-defined POEOMA copolymers with middle disulfides and terminal RAFT species. They were then used as precursors for thiol-disulfide polyexchange induced by aminolysis and reductive reaction followed by oxidation: these polydisulfides with different molecular weights and end groups exhibited tunable thermoresponsive properties and thiol-responsive degradation.

Cover Picture: pH‐ and Redox‐Responsive Polysaccharide‐Based Microcapsules with Autofluorescence for Biomedical Applications (Chem. Eur. J. 11/2012)

Autofluorescent microcapsules with pH- and redox-responsive properties for pinpointed intracellular delivery were assembled by covalent cross-linking of polysaccharide derivative alginate dialdehyde (ADA) and cystamine dihydrochloride (CM) through layer-by-layer (LBL) technique. The simple and versatile method could be extended to other polysaccharide derivatives for the fabrication of autofluorescent nano- and micromaterials with dual stimuli response for biomedical applications. For more information see the Full Paper by J. Li et al. on page 3185 ff.

PH‐ and Redox‐Responsive Polysaccharide‐Based Microcapsules with Autofluorescence for Biomedical Applications

Autofluorescent microcapsules were assembled by covalent cross-linking of polysaccharide alginate dialdehyde (ADA) derivative and cystamine dihydrochloride (CM) through a layer-by-layer (LBL) technique. The formulated Schiff base and disulfide bonds render capsules with pH- and redox-responsive properties for pinpointed intracellular delivery based on the physiological difference between intracellular and extracellular environments. This simple and versatile method could be extended to other polysaccharide derivatives for the fabrication of autofluorescent nano- and micromaterials with dual stimuli response for biomedical applications.

Molecular Self‐Assembly of a Homopolymer: An Alternative To Fabricate Drug‐Delivery Platforms for Cancer Therapy

The best of both worlds: A novel amphiphilic homopolymer synthesized from a monomer consisting of a hydrophobic group (see picture, red) and a hydrophilic moiety (green) self-assembles in aqueous solution. The resulting micelles have a multi-core/shell structure and exhibit smart redox-responsive properties, thus providing a favorable drug delivery platform for cancer therapy. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Preparation of a Rapidly Forming Poly(ferrocenylsilane)‐Poly(ethylene glycol)‐based Hydrogel by a Thiol‐Michael Addition Click Reaction

The synthesis of a rapidly forming redox responsive poly(ferrocenylsilane)-poly(ethylene glycol) (PFS-PEG)-based hydrogel is described, achieved by a thiol-Michael addition click reaction. PFS bearing acrylate side groups (PFS-acryl) was synthesized by side group modification of poly(ferrocenyl(3-iodopropyl)methylsilane) (PFS-I) and characterized by (1) H NMR, (13) C NMR, and FT-IR spectroscopy. The equilibrium swelling ratio, morphology, rheology, and redox responsive properties of the PFS-PEG-based hydrogel are reported.

One-Pot Preparation of Ferrocene-Functionalized Polymer Brushes on Gold Substrates by Combined Surface-Initiated Atom Transfer Radical Polymerization and “Click Chemistry”

A gold substrate with surface-grafted ferrocene functional polymer brushes, or Au-g-PFTMA surface [PFTMA = poly(5-ferrocene-triazolyl methacrylate)], was prepared by a combination of surface-initiated atom transfer radical polymerization (SI-ATRP) and "click chemistry" in one pot, in the presence of 2-azidoethyl methacrylate (AzEMA), ethynyl ferrocene, CuBr catalyst, CuBr(2) deactivator, and pentamethyldiethylenetriamine ligand. Thus, SI-ATRP of AzEMA from the Au substrate (the "grafting from" process) and click chemistry of the ethynyl ferrocene to the azide functional group of AzEMA (the "grafting to" process) proceeded simultaneously to produce the functional PFTMA brushes on the Au surface. Kinetic studies suggest that the reaction involving simultaneous SI-ATRP and click chemistry is still consistent with a controlled/"living" process. The composition and physical properties of the modified gold surface were analyzed by X-ray photoelectron spectroscopy, water contact angle measurement, and cyclic voltammetry. The redox-responsive properties of the ferrocene-functionalized polymer brushes on the Au-g-PFTMA surface were demonstrated in the reversible loading-unloading step of the β-cyclodextrin polymer via host-guest interaction.

Preparation of novel organometallic derivatives of cholesterol and their gel-formation properties

Ferrocene (Fc) as a pendant structure has been intentionally introduced into three dicholesteryl derivatives of a LS 2 type structure, where L denotes a linker and S stands for a steroidal unit. The compounds as designed are denoted as 1, 2 and 3 according to the number of hydrogen-bonding sites in the linkers. Gelation tests revealed that 1 gelates none of the 34 solvents tested, 2 gelates some of the alkanes, and 3 gelates only cyclohexane and DMSO. Importantly, the gel system of 2/ n-decane exhibits a sol–gel phase transition upon thermal, ultrasonic, mechanical or even chemical treatments. FTIR, temperature- and concentration-dependent 1H NMR spectroscopy measurements revealed that intermolecular hydrogen-bonding is one of the driving forces for gel formation. XRD analysis demonstrated that 2 exists in a stretched conformation and aggregates into layered structure in its n-decane and cyclohexane gels. Far from that expected, introduction of Fc unit does not bring the redox responsive properties to the gel systems.