Reversible Protein Capture and Release by Redox-Responsive Hydrogel in Microfluidics

Stimuli-responsive hydrogels have a wide range of potential applications in microfluidics, which has drawn great attention. Double cross-linked hydrogels are very well suited for this application as they offer both stability and the required responsive behavior. Here, we report the integration of poly(N-isopropylacrylamide) (PNiPAAm) hydrogel with a permanent cross-linker (N,N′-methylenebisacrylamide, BIS) and a redox responsive reversible cross-linker (N,N′-bis(acryloyl)cystamine, BAC) into a microfluidic device through photopolymerization. Cleavage and re-formation of disulfide bonds introduced by BAC changed the cross-linking densities of the hydrogel dots, making them swell or shrink. Rheological measurements allowed for selecting hydrogels that withstand long-term shear forces present in microfluidic devices under continuous flow. Once implemented, the thiol-disulfide exchange allowed the hydrogel dots to successfully capture and release the protein bovine serum albumin (BSA). BSA was labeled with rhodamine B and functionalized with 2-(2-pyridyldithio)-ethylamine (PDA) to introduce disulfide bonds. The reversible capture and release of the protein reached an efficiency of 83.6% in release rate and could be repeated over 3 cycles within the microfluidic device. These results demonstrate that our redox-responsive hydrogel dots enable the dynamic capture and release of various different functionalized (macro)molecules (e.g., proteins and drugs) and have a great potential to be integrated into a lab-on-a-chip device for detection and/or delivery.

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Conjugation of Doxorubicin to siRNA Through Disulfide-based Self-immolative Linkers

Molecules ◽

10.3390/molecules25112714 ◽

2020 ◽

Vol 25 (11) ◽

pp. 2714 ◽

Cited By ~ 3

Author(s):

Florian Gauthier ◽

Jean-Rémi Bertrand ◽

Jean-Jacques Vasseur ◽

Christelle Dupouy ◽

Françoise Debart

Keyword(s):

Disulfide Bonds ◽

Chemotherapeutic Drugs ◽

Exchange Reactions ◽

Disulfide Exchange ◽

Physiological Conditions ◽

Drug Conjugates ◽

Reducing Conditions ◽

Redox Responsive ◽

Covalent Interactions ◽

Premature Release

Co-delivery systems of siRNA and chemotherapeutic drugs have been developed as an attractive strategy to optimize the efficacy of chemotherapy towards cancer cells with multidrug resistance. In these typical systems, siRNAs are usually associated to drugs within a carrier but without covalent interactions with the risk of a premature release and degradation of the drugs inside the cells. To address this issue, we propose a covalent approach to co-deliver a siRNA-drug conjugate with a redox-responsive self-immolative linker prone to intracellular glutathione-mediated disulfide cleavage. Herein, we report the use of two disulfide bonds connected by a pentane spacer or a p-xylene spacer as self-immolative linker between the primary amine of the anticancer drug doxorubicin (Dox) and the 2′-position of one or two ribonucleotides in RNA. Five Dox-RNA conjugates were successfully synthesized using two successive thiol-disulfide exchange reactions. The Dox-RNA conjugates were annealed with their complementary strands and the duplexes were shown to form an A-helix sufficiently stable under physiological conditions. The enzymatic stability of Dox-siRNAs in human serum was enhanced compared to the unmodified siRNA, especially when two Dox are attached to siRNA. The release of native Dox and RNA from the bioconjugate was demonstrated under reducing conditions suggesting efficient linker disintegration. These results demonstrate the feasibility of making siRNA-drug conjugates via disulfide-based self-immolative linkers for potential therapeutic applications.

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Pyridyl disulfide-based thiol–disulfide exchange reaction: shaping the design of redox-responsive polymeric materials

Polymer Chemistry ◽

10.1039/d0py01215g ◽

2020 ◽

Vol 11 (48) ◽

pp. 7603-7624

Author(s):

Ismail Altinbasak ◽

Mehmet Arslan ◽

Rana Sanyal ◽

Amitav Sanyal

Keyword(s):

Exchange Reaction ◽

Functional Materials ◽

Polymeric Materials ◽

Disulfide Exchange ◽

Redox Responsive ◽

Synthetic Approaches

This review provides an overview of synthetic approaches utilized to incorporate the thiol-reactive pyridyl-disulfide motif into various polymeric materials, and briefly highlights its utilization to obtain functional materials.

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Dynamic Manipulation of THz Waves Enabled by Phase-Transition VO2 Thin Film

Nanomaterials ◽

10.3390/nano11010114 ◽

2021 ◽

Vol 11 (1) ◽

pp. 114

Author(s):

Chang Lu ◽

Qingjian Lu ◽

Min Gao ◽

Yuan Lin

Keyword(s):

Optical Methods ◽

Stimuli Responsive ◽

Device Structure ◽

Current State ◽

Insulator Metal Transition ◽

Potential Applications ◽

Fs Laser ◽

External Stimuli ◽

Thz Applications ◽

Thz Waves

The reversible and multi-stimuli responsive insulator-metal transition of VO2, which enables dynamic modulation over the terahertz (THz) regime, has attracted plenty of attention for its potential applications in versatile active THz devices. Moreover, the investigation into the growth mechanism of VO2 films has led to improved film processing, more capable modulation and enhanced device compatibility into diverse THz applications. THz devices with VO2 as the key components exhibit remarkable response to external stimuli, which is not only applicable in THz modulators but also in rewritable optical memories by virtue of the intrinsic hysteresis behaviour of VO2. Depending on the predesigned device structure, the insulator-metal transition (IMT) of VO2 component can be controlled through thermal, electrical or optical methods. Recent research has paid special attention to the ultrafast modulation phenomenon observed in the photoinduced IMT, enabled by an intense femtosecond laser (fs laser) which supports “quasi-simultaneous” IMT within 1 ps. This progress report reviews the current state of the field, focusing on the material nature that gives rise to the modulation-allowed IMT for THz applications. An overview is presented of numerous IMT stimuli approaches with special emphasis on the underlying physical mechanisms. Subsequently, active manipulation of THz waves through pure VO2 film and VO2 hybrid metamaterials is surveyed, highlighting that VO2 can provide active modulation for a wide variety of applications. Finally, the common characteristics and future development directions of VO2-based tuneable THz devices are discussed.

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pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00895-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

He Wang ◽

Wenwen Shi ◽

Danning Zeng ◽

Qiudi Huang ◽

Jiacui Xie ◽

...

Keyword(s):

Lung Cancer ◽

Drug Resistance ◽

Disulfide Bonds ◽

Cancer Metastasis ◽

Mitochondrial Outer Membrane ◽

Drug Resistant ◽

Redox Responsive ◽

Dimethylmaleic Anhydride ◽

Extended Circulation ◽

Mitochondria Targeting

Abstract Background Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown. Results Acid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells. Conclusions These promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment. Graphic Abstarct

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Combining Dextran Conjugates with Stimuli-Responsive and Folate-Targeting Activity: A New Class of Multifunctional Nanoparticles for Cancer Therapy

Nanomaterials ◽

10.3390/nano11051108 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1108

Author(s):

Manuela Curcio ◽

Alessandro Paolì ◽

Giuseppe Cirillo ◽

Sebastiano Di Pietro ◽

Martina Forestiero ◽

...

Keyword(s):

Cancer Therapy ◽

Drug Release ◽

Metastatic Cancer ◽

Stimuli Responsive ◽

Cancer Disease ◽

New Class ◽

Self Assembling ◽

Redox Responsive ◽

Potential Applicability ◽

Mean Size

Nanoparticles with active-targeting and stimuli-responsive behavior are a promising class of engineered materials able to recognize the site of cancer disease, targeting the drug release and limiting side effects in the healthy organs. In this work, new dual pH/redox-responsive nanoparticles with affinity for folate receptors were prepared by the combination of two amphiphilic dextran (DEX) derivatives. DEXFA conjugate was obtained by covalent coupling of the polysaccharide with folic acid (FA), whereas DEXssPEGCOOH derived from a reductive amination step of DEX was followed by condensation with polyethylene glycol 600. After self-assembling, nanoparticles with a mean size of 50 nm, able to be destabilized in acidic pH and reducing media, were obtained. Doxorubicin was loaded during the self-assembling process, and the release experiments showed the ability of the proposed system to modulate the drug release in response to different pH and redox conditions. Finally, the viability and uptake experiments on healthy (MCF-10A) and metastatic cancer (MDA-MB-231) cells proved the potential applicability of the proposed system as a new drug vector in cancer therapy.

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Thermo- and Photoresponsive Behaviors of Dual-Stimuli-Responsive Organogels Consisting of Homopolymers of Coumarin-Containing Methacrylate

Polymers ◽

10.3390/polym13030329 ◽

2021 ◽

Vol 13 (3) ◽

pp. 329

Author(s):

Seidai Okada ◽

Eriko Sato

Keyword(s):

Functional Group ◽

Solution Temperature ◽

Stimuli Responsive ◽

Critical Solution Temperature ◽

Equilibrium Degree ◽

Stimuli Responsive Polymers ◽

Responsive Polymers ◽

Dual Functional ◽

Wide Range ◽

Increasing Temperature

Coumarin-containing vinyl homopolymers, such as poly(7-methacryloyloxycoumarin) (P1a) and poly(7-(2′-methacryloyloxyethoxy)coumarin) (P1b), show a lower critical solution temperature (LCST) in chloroform, which can be controlled by the [2 + 2] photochemical cycloaddition of the coumarin moiety, and they are recognized as monofunctional dual-stimuli-responsive polymers. A single functional group of monofunctional dual-stimuli-responsive polymers responds to dual stimuli and can be introduced more uniformly and densely than those of dual-functional dual-stimuli-responsive polymers. In this study, considering a wide range of applications, organogels consisting of P1a and P1b, i.e., P1a-gel and P1b-gel, respectively, were synthesized, and their thermo- and photoresponsive behaviors in chloroform were investigated in detail. P1a-gel and P1b-gel in a swollen state (transparent) exhibited phase separation (turbid) through a temperature jump and reached a shrunken state (transparent), i.e., an equilibrium state, over time. Moreover, the equilibrium degree of swelling decreased non-linearly with increasing temperature. Furthermore, different thermoresponsive sites were photopatterned on the organogel through the photodimerization of the coumarin unit. The organogels consisting of homopolymers of coumarin-containing methacrylate exhibited unique thermo- and photoresponsivities and behaved as monofunctional dual-stimuli-responsive organogels.

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A Slot-Die Technique for the Preparation of Continuous, High-Area, Chitosan-Based Thin Films

Polymers ◽

10.3390/polym13101566 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1566

Author(s):

Oliver J. Pemble ◽

Maria Bardosova ◽

Ian M. Povey ◽

Martyn E. Pemble

Keyword(s):

Thin Films ◽

Mechanical Properties ◽

High Volume ◽

Mechanical Anisotropy ◽

Diverse Range ◽

Direction Parallel ◽

High Area ◽

Wide Range ◽

Slot Die ◽

Potential Applications

Chitosan-based films have a diverse range of potential applications but are currently limited in terms of commercial use due to a lack of methods specifically designed to produce thin films in high volumes. To address this limitation directly, hydrogels prepared from chitosan, chitosan-tetraethoxy silane, also known as tetraethyl orthosilicate (TEOS) and chitosan-glutaraldehyde have been used to prepare continuous thin films using a slot-die technique which is described in detail. By way of preliminary analysis of the resulting films for comparison purposes with films made by other methods, the mechanical strength of the films produced was assessed. It was found that as expected, the hybrid films made with TEOS and glutaraldehyde both show a higher yield strength than the films made with chitosan alone. In all cases, the mechanical properties of the films were found to compare very favorably with similar measurements reported in the literature. In order to assess the possible influence of the direction in which the hydrogel passes through the slot-die on the mechanical properties of the films, testing was performed on plain chitosan samples cut in a direction parallel to the direction of travel and perpendicular to this direction. It was found that there was no evidence of any mechanical anisotropy induced by the slot die process. The examples presented here serve to illustrate how the slot-die approach may be used to create high-volume, high-area chitosan-based films cheaply and rapidly. It is suggested that an approach of the type described here may facilitate the use of chitosan-based films for a wide range of important applications.

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Health Benefits of Uses and Applications of Moringa oleifera in Bakery Products

Plants ◽

10.3390/plants10020318 ◽

2021 ◽

Vol 10 (2) ◽

pp. 318

Author(s):

Paula García Milla ◽

Rocío Peñalver ◽

Gema Nieto

Keyword(s):

Moringa Oleifera ◽

Essential Amino Acids ◽

Bakery Products ◽

Unani Medicine ◽

Functional Value ◽

Organoleptic Characteristics ◽

Wide Range ◽

Potential Applications ◽

Medicinal Properties ◽

Excellent Source

Moringa oleifera belongs to the Moringaceae family and is the best known of the native Moringa oleifera genus. For centuries, it has been used as a system of Ayurvedic and Unani medicine and has a wide range of nutritional and bioactive compounds, including proteins, essential amino acids, carbohydrates, lipids, fibre, vitamins, minerals, phenolic compounds, phytosterols and others. These characteristics allow it to have pharmacological properties, including anti-diabetic, anti-inflammatory, anticarcinogenic, antioxidant, cardioprotective, antimicrobial and hepatoprotective properties. The entire Moringa oleifera plant is edible, including its flowers, however, it is not entirely safe, because of compounds that have been found mainly in the root and bark, so the leaf was identified as the safest. Moringa oleifera is recognised as an excellent source of phytochemicals, with potential applications in functional and medicinal food preparations due to its nutritional and medicinal properties; many authors have experimented with incorporating it mainly in biscuits, cakes, brownies, meats, juices and sandwiches. The results are fascinating, as the products increase their nutritional value; however, the concentrations cannot be high, as this affects the organoleptic characteristics of the supplemented products. The aim of this study is to review the application of Moringa oleifera in bakery products, which will allow the creation of new products that improve their nutritional and functional value.

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Sporulation in solventogenic and acetogenic clostridia

Applied Microbiology and Biotechnology ◽

10.1007/s00253-021-11289-9 ◽

2021 ◽

Author(s):

Mamou Diallo ◽

Servé W. M. Kengen ◽

Ana M. López-Contreras

Keyword(s):

Current Knowledge ◽

Carbon Sources ◽

Cost Effective ◽

Biotechnological Production ◽

Key Points ◽

Wide Range ◽

Potential Applications ◽

A Cell ◽

Sporulation Initiation ◽

Solventogenic Clostridia

AbstractThe Clostridium genus harbors compelling organisms for biotechnological production processes; while acetogenic clostridia can fix C1-compounds to produce acetate and ethanol, solventogenic clostridia can utilize a wide range of carbon sources to produce commercially valuable carboxylic acids, alcohols, and ketones by fermentation. Despite their potential, the conversion by these bacteria of carbohydrates or C1 compounds to alcohols is not cost-effective enough to result in economically viable processes. Engineering solventogenic clostridia by impairing sporulation is one of the investigated approaches to improve solvent productivity. Sporulation is a cell differentiation process triggered in bacteria in response to exposure to environmental stressors. The generated spores are metabolically inactive but resistant to harsh conditions (UV, chemicals, heat, oxygen). In Firmicutes, sporulation has been mainly studied in bacilli and pathogenic clostridia, and our knowledge of sporulation in solvent-producing or acetogenic clostridia is limited. Still, sporulation is an integral part of the cellular physiology of clostridia; thus, understanding the regulation of sporulation and its connection to solvent production may give clues to improve the performance of solventogenic clostridia. This review aims to provide an overview of the triggers, characteristics, and regulatory mechanism of sporulation in solventogenic clostridia. Those are further compared to the current knowledge on sporulation in the industrially relevant acetogenic clostridia. Finally, the potential applications of spores for process improvement are discussed.Key Points• The regulatory network governing sporulation initiation varies in solventogenic clostridia.• Media composition and cell density are the main triggers of sporulation.• Spores can be used to improve the fermentation process.

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Click Chemistry Enabling Covalent and Non-Covalent Modifications of Graphene with (Poly)saccharides

Polymers ◽

10.3390/polym13010142 ◽

2020 ◽

Vol 13 (1) ◽

pp. 142

Author(s):

Hu Li ◽

Raffaello Papadakis

Keyword(s):

Click Chemistry ◽

Life Science ◽

Environmental Applications ◽

Energy Materials ◽

Sensors And Actuators ◽

Polar Solvents ◽

Wide Range ◽

Potential Applications ◽

Covalent Modifications

Graphene is a material with outstanding properties and numerous potential applications in a wide range of research and technology areas, spanning from electronics, energy materials, sensors, and actuators to life-science and many more. However, the insolubility and poor dispersibility of graphene are two major problems hampering its use in certain applications. Tethering mono-, di-, or even poly-saccharides on graphene through click-chemistry is gaining more and more attention as a key modification approach leading to new graphene-based materials (GBM) with improved hydrophilicity and substantial dispersibility in polar solvents, e.g., water. The attachment of (poly)saccharides on graphene further renders the final GBMs biocompatible and could open new routes to novel biomedical and environmental applications. In this review, recent modifications of graphene and other carbon rich materials (CRMs) through click chemistry are reviewed.

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