Diselenide-containing Polymers Research Articles

Diselenide-Containing Polymer Based on New Antitumor Mechanism as Efficient GSH Depletion Agent for Ferroptosis Therapy.

Glutathione (GSH) depletion-induced ferroptosis has emerged as a promising treatment for malignant cancer. It works by inactivating glutathione peroxidase 4 (GPX4) and facilitating lipid peroxidation. However, effectively delivering inducers and depleting intracellular GSH remains challenging due to the short half-lives and high hydrophobicity of small-molecule ferroptosis inducers. These inducers often require additional carriers. Herein, diselenide-containing polymers can consume GSH to induce ferroptosis for pancreatic cancer therapy. The diselenide bonds are controllably built into the backbone of the polycarbonate with a targeting peptide CRGD (Cys-Arg-Gly-Asp), which allows for self-assembly into stable nanoparticles (denoted CRNSe) for self-delivery. Significantly, at a concentration of 12 µg mL-1, CRNSe binds to the active site cysteine of GSH resulting in a thorough depletion of GSH. In contrast, the disulfide-containing analog only causes a slight decrease in GSH level. Moreover, the depletion of GSH inactivates GPX4, ultimately inducing ferroptosis due to the accumulation of lipid peroxide in BxPC-3 cells. Both in vitro and in vivo studies have demonstrated that CRNSe exhibits potent tumor suppressive ability with few side effects on normal tissue. This study validates the anti-tumor mechanism of diselenide-containing polymers in addition to apoptosis and also provides a new strategy for inherently inducing ferroptosis in cancer therapy.

CO/chemosensitization/antiangiogenesis synergistic therapy with H2O2-responsive diselenide-containing polymer

Carbon monoxide (CO) therapy and antiangiogenesis therapy (AAT) are regarded as promising approaches for cancer treatment. However, the poor tumor targeting ability and inevitable side effects prevent their clinical application. In this study, we developed H2O2-responsive diselenide-containing micelles that combined CO therapy with chemosensitization therapy and AAT in a single system. Under the interaction of intratumoral H2O2, CO and gemcitabine (GEM) were released in situ from the micelles to reduce side effects, and CO significantly sensitized the chemotherapeutic effect of GEM by elevating the level of reactive oxygen species (ROS) in human gastric cancer AGS cells. Furthermore, diselenide bonds in the micelles were oxidized to seleninic acid in organic form, which suppressed the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) to realize AAT. This study provides an integrated solution to combine CO therapy with chemosensitization therapy and AAT together with good biocompatibility.

Semi-convertible Hydrogel Enabled Photoresponsive Lubrication

Summary A semi-convertible hydrogel with reversible photoresponsive supramolecular lubricating ability is demonstrated by integrating a responsive supramolecular system of α-cyclodextrins/polyethylene glycol (α-CD/PEG) and competitive guest 1-[p-(phenylazo)benzyl]pyridinium bromide (AzoPB) within a poly(vinyl alcohol) (PVA) and polyacrylamide (PAAm) framework. The competitive host-guest interaction between α-CD/PEG supramolecular network and AzoPB after UV and visible-light irradiation enables the appearance and disappearance of the sol-state layer on the hydrogel surface while the PVA and PAAm consistently keeps the framework. This semi-convertible process realizes the reversible photoresponsive lubricating ability and variable toughness. We envision that this finding will offer a possible way for fabricating novel smart devices far beyond lubrication, leading to an emerging branch of interdisciplinary materials science that integrates supramolecular chemistry, hydrogel, and surface science.

Diselenide-Linked Polymers under Sonication.

A series of Se-Se-linked polystyrenes have been synthesized and subjected to pulse sonication. Comprehensive investigations based on GPC measurements, derivatization experiments, and EPR spectroscopy verify the sonication-induced bond scission and metathesis of these polymeric diselenides. The metathesis kinetics and energy conversion efficiency by different stimuli including heating, light, and sonication are compared, which demonstrate that sonication can offer an alternative way to break the Se-Se bond and realize selective metathesis reactions between diselenide-linked polymers and small molecules. This fundamental study on sonochemistry of diselenide-centered polymers expands our knowledge of diselenide chemistry and mechanochemistry of dynamic covalent mechanophores, which may greatly advance the applications of diselenide-containing polymers.

In My Element: Selenium

<i>In My Element</i>: Selenium

Syntheses of diselenide-containing dynamic polymers and their application in polymer alloys

The diselenide-containing polycarbonate ((PTMCSe)2) and diselenide-containing poly(ε-caprolactone) ((PCLSe)2) were synthesized by the ring opening polymerization using a new compound of di-(1-hydroxypropyl) diselenide ((HOC3H6Se)2) as initiator. The dynamic properties of these diselenide-containing polymers were revealed by a series of diselenide exchange reactions, which could be realized under visible irradiation at room temperature. As the result of the diselenide exchange between (PTMCSe)2 and (PCLSe)2, a di-block polymer (PCLSeSePTMC) was formed in (PTMCSe)2/(PCLSe)2 alloy. Taking advantage of the diselenide exchange, the compatibility and miscibility of (PTMCSe)2/(PCLSe)2 alloy was significantly improved by the exchange product (PCLSeSePTMC) which acted as polymeric compatilizer. This novel concept may be applied in other polymer alloys containing dynamic covalent polymers.

Enhancement of the stimuli-responsiveness and photo-stability of dynamic diselenide bonds and diselenide-containing polymers by neighboring aromatic groups

The investigation of dynamic covalent bonds, which are exchangeable upon exposure to mild stimuli, represents an important topic toward the development of various advanced systems. Herein, we report enhanced dynamic properties for diselenide bonds that carry neighboring aromatic rings compared to their aliphatic derivatives. The bond exchange reactions in low-molecular-weight and linear polymer systems exhibit a faster equilibration for the aromatic diselenides relative to their aliphatic derivatives either under exposure to visible light or to heating (60 °C) in the dark. This behavior was rationalized in terms of i) the conjugated structures that contribute to the higher sensitivity toward longer-wavelength light, and ii) the homolytic dissociability via resonance stabilization of the dissociated radicals. Quantitative tensile measurements on cross-linked polyurethane in the bulk state revealed an improved healing capacity for those polymers that contain aromatic diselenide moieties relative to those that contain aliphatic diselenides. Furthermore, bulk cross-linked polymers and small molecules that contain aromatic diselenides exhibit higher photo-stability against UV light, demonstrating the potential of these bonds as stable and easy-to-handle dynamic covalent bonds.

Selenium-Functionalized Graphene Oxide That Can Modulate the Balance of Reactive Oxygen Species.

Graphene oxide (GO) is an important two-dimensional material since it is water-soluble and can be functionalized to adapt to different applications. However, the current covalent functionalization methods usually require hash conditions, long duration, and sometimes even multiple steps, while noncovalent functionalization is inevitably unstable, especially under a physiological environment where competing species exist. Diselenide bond is a dynamic covalent bond and can respond to both redox conditions and visible light irradiation in a sensitive manner. Thus, in this work by combining the stimuli response of diselenide bond and the oxidative/radical attackable nature of GO, we achieved the in situ covalent functionalization of GO simply by stirring GO with diselenide-containing molecules in aqueous solution. The covalent functionalization was proved by Fourier transform infrared, time-of-flight secondary ion mass spectrometry, atomic force microscopy, thermogravimetric analysis, and so forth, and the functionalization mechanism was deduced to involve both redox reaction and radical addition reaction according to the X-ray photoelectron spectrscopy, atomic emission spectroscopy, and Raman spectroscopy. Moreover, we modified GO with a biocompatible diselenide-containing polymer (mPEGSe)2 and found selenium-functionalized GO could modulate the balance of reactive oxygen species (ROS). GOSe could decrease ROS level by accelerating the reduction of peroxides when the ROS concentration is high while boosting the ROS level by in situ generating ROS when its concentration is relatively low.

Selenolactone as a Building Block toward Dynamic Diselenide-Containing Polymer Architectures with Controllable Topology.

A versatile protocol for the synthesis of a variety of multiresponsive diselenide-containing polymeric architectures was investigated. It consists of a one-pot, two-step process with the generation of a selenol by in situ nucleophilic ring opening of selenolactone with a broad range of amine-containing structures, followed by the transformation of the obtained compounds to the corresponding diselenide through a spontaneous oxidation coupling reaction. After elaboration of this one-pot reaction, a number of routes based on selenolactones have been developed for the successful synthesis of functional, linear, branched, cyclic, and cross-linked polymers via a mild, straightforward process. Moreover, the polymer end groups can be easily modified by changing the ratio of amine and selenolactone or sequential Michael addition of selenol to the methacrylic ester. At last, the self-healing properties of the diselenide-containing networks were determined by exposing a cut sample of the polymer to UV light.

Diselenide-Labeled Cyclic Polystyrene with Multiple Responses: Facile Synthesis, Tunable Size, and Topology.

Diselenide-containing polymers have attracted more and more attention due to their redox sensitivity and bioapplication. In this work, a bifunctional diselenocarbonate is prepared and used to mediate the reversible addition-fragmentation chain transfer (RAFT) polymerization, producing α,ω-selenocarbonate-labeled telechelic polystyrene. Based on effective aminolysis of the terminal selenocarbonates and the followed spontaneous oxidation coupling reaction of diselenols, monoblock cyclic polystyrene linked by one diselenide bond and multiblock cyclic copolymer linked by several diselenide bonds are prepared by manipulating the concentration of α,ω-telechelic polystyrene in solution. The progress of aminolysis and the subsequent spontaneous oxidation of selenols to diselenides are monitored by UV-vis, gel permeation chromatography (GPC), and NMR characterizations, confirming the cyclic topologies of the resultant polymers (monocyclic or multiblock cyclic polymer). The monoblock cyclic or multiblock polymers show redox sensitivity, which can be converted to linear polymer by reducing or oxidizing agent. Moreover, the obtained monoblock cyclic polymer or multiblock cyclic copolymer can be transformed to each other under UV irradiation by adjusting the concentration of the cyclic polystyrene. For the first time, this work provides an alternative and promising approach to realize the topological transformation of polymers by installing multiresponsive diselenide moities into the backbone of cyclic polymer.

Diselenide covalent chemistry at the interface: stabilizing an asymmetric diselenide-containing polymer via micelle formation

Diselenide metathesis at an oil/water interface has been demonstrated and an asymmetric diselenide-containing polymer was stabilized via the micelle formation method.

A Straightforward Method for Preparing Well-Defined Responsive Diselenide-Containing Polymers Based on ATRP.

Diselenide-containing polymers are facilely synthesized from polymers prepared by atom transfer radical polymerization (ATRP). Benefiting from the ATRP technology, this protocol provides a flexible route for controlling the polymer structure, which allows for a great variety of architectures of selenium-containing polymer materials for applications in various fields. The oxidative and reductive responsive behavior of the obtained diselenide-containing polymers is also investigated.

ChemInform Abstract: The Combination of Chemotherapy and Radiotherapy Towards More Efficient Drug Delivery

AbstractReview: 25 refs.

The Combination of Chemotherapy and Radiotherapy towards More Efficient Drug Delivery

Research on anticancer therapies has advanced significantly in recent years. New therapeutic platforms that can further improve the health of patients are still highly demanded. We propose the idea of combining regular chemotherapy with radiation therapy to minimize side effects as well as increase drug-delivery efficiency. In this Focus Review, we seek to provide an overview of recent advances that can combine chemotherapy and radiotherapy. We begin by reviewing the current state of systems that can combine chemotherapy and gamma radiation. Among them, diselenide-containing polymers are highlighted as sensitive drug-delivery vehicles that can disassemble under gamma radiation. Then X-ray responsive materials as promising alternative systems are summarized, including X-ray responsive drug-delivery vehicles, prodrugs that can be activated by X-rays, and radiation-site-targeting systems. Finally, we describe strategies that involve phototherapies.