Heteropoly acid-driven assembly of glutathione into redox-responsive underwater adhesive

2020 ◽  
Vol 56 (75) ◽  
pp. 11034-11037
Author(s):  
Xiaohuan Liu ◽  
Jing Xu ◽  
Xiaoming Xie ◽  
Zhiyuan Ma ◽  
Tingting Zheng ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Heteropoly Acid ◽  
Redox Responsive ◽  
Reversible Formation

A glutathione-based underwater adhesive with dynamic attachment/detachment behaviour was achieved via the reversible formation and breakage of disulfide bonds of glutathione.

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

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

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

Polymers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 267
Author(s):  
Chen Jiao ◽  
Franziska Obst ◽  
Martin Geisler ◽  
Yunjiao Che ◽  
Andreas Richter ◽  
...  
Keyword(s):  
Microfluidic Device ◽  
Disulfide Bonds ◽  
Stimuli Responsive ◽  
Disulfide Exchange ◽  
Protein Capture ◽  
Wide Range ◽  
Redox Responsive ◽  
Potential Applications ◽  
Capture And Release ◽  
Cross Linker

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.

scholarly journals Impact of key residues within chloroplast thioredoxin-f on recognition for reduction and oxidation of target proteins

2019 ◽  
Vol 294 (46) ◽  
pp. 17437-17450 ◽  
Author(s):  
Yuichi Yokochi ◽  
Kazunori Sugiura ◽  
Kazuhiro Takemura ◽  
Keisuke Yoshida ◽  
Satoshi Hara ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Redox Regulation ◽  
Target Recognition ◽  
Dynamics Simulation ◽  
Target Proteins ◽  
Specific Target ◽  
Redox Responsive ◽  
Key Residues ◽  
Protein Reduction ◽  
The Impact

Thioredoxin (Trx) is a redox-responsive protein that modulates the activities of its target proteins mostly by reducing their disulfide bonds. In chloroplasts, five Trx isoforms (Trx-f, Trx-m, Trx-x, Trx-y, and Trx-z) regulate various photosynthesis-related enzymes with distinct target selectivity. To elucidate the determinants of the target selectivity of each Trx isoform, here we investigated the residues responsible for target recognition by Trx-f, the most well-studied chloroplast-resident Trx. As reported previously, we found that positively-charged residues on the Trx-f surface are involved in the interactions with its targets. Moreover, several residues that are specifically conserved in Trx-f (e.g. Cys-126 and Thr-158) were also involved in interactions with target proteins. The validity of these residues was examined by the molecular dynamics simulation. In addition, we validated the impact of these key residues on target protein reduction by studying (i) Trx-m variants into which we introduced the key residues for Trx-f and (ii) Trx-like proteins, named atypical Cys His-rich Trx 1 (ACHT1) and ACHT2a, that also contain these key residues. These artificial or natural protein variants could reduce Trx-f–specific targets, indicating that the key residues for Trx-f are critical for Trx-f–specific target recognition. Furthermore, we demonstrate that ACHT1 and ACHT2a efficiently oxidize some Trx-f–specific targets, suggesting that its target selectivity also contributes to the oxidative regulation process. Our results reveal the key residues for Trx-f–specific target recognition and uncover ACHT1 and ACHT2a as oxidation factors of their target proteins, providing critical insight into redox regulation of photosynthesis.

scholarly journals Tuning Paclitaxel Release Behavior Using Dually-Responsive Nanomicellar Assemblies with Multiple Diselenide/Disulfide Linkages

2021 ◽  
Author(s):  
Jingwen Xu ◽  
Xiangji Yan ◽  
Yue Zhang ◽  
Kangsheng Tu ◽  
Wen Shen ◽  
...  
Keyword(s):  
Disulfide Bonds ◽  
Slow Release ◽  
Gel Permeation Chromatography ◽  
Mass Ratio ◽  
Drug Bioavailability ◽  
Chemical Structures ◽  
Disulfide Linkages ◽  
Vis Spectroscopy ◽  
Redox Responsive

Abstract Background: There are many reasons that lead to the failure of cancer chemotherapy, such as uncontrolled drug release, low drug utilization, and severe side effects. Methods: To overcome these obstacles, we designed two kinds of copolymers with thermal and redox-responsive properties containing multiple diselenide/disulfide bonds polyethylene glycol -alt- diselenodipropionate/disulfhydryldipropionate-b-poly(N-isopropylacrylamide) (abbreviated as PEG-alt-DSeDP-b-PNIPAM and PEG-alt-DSDP-b-PNIPAM) by alternative esterification and following atom transfer radical polymerization. Afterward, these prepared copolymers were mixed with the mass ratio of 8:0, 5:3, 3:5, 0:8 (denoted as S1, S2, S3, and S4, respectively), and self-assembled with paclitaxel (PTX) to obtain PTX-loaded S1, S2, S3, and S4 nanomicellar assemblies, aiming to realize PTX controlled and on-demand release. Results: The chemical structures of these two copolymers were characterized by gel permeation chromatography (GPC), indicating eight diselenide/disulfide linkages and eight PEG units were contained in these copolymers. Moreover, the thermal-responsive property was detected by UV-vis spectroscopy, meanwhile, the redox-responsive property was observed by TEM in the presence of 10 mM glutathione (GSH). We found that 76.90% of PTX was released from S1 nanomicelles within 23 h. In contrast, this percentage decreased to 64.53% for S4 nanomicelles even the incubation time prolonged to 82 h, indicating explosive and slow release behaviors of S1 and S4 nanomicelles, respectively. In addition, gradually decreased fluorescence intensity around the cellular nucleus was occurred from S1 to S4 orderly, which was consistent with cellular uptake and in vivo anti-tumor experiments. Conclusion: This work not only provides a strategy for the controlled and effective release of PTX, but also improves drug bioavailability in cancer treatment.

Reversible formation of multiple stimuli-responsive polymeric materials through processing control of trifunctional amphiphilic molecules

2020 ◽  
Vol 56 (57) ◽  
pp. 7881-7884
Author(s):  
Takahiro Muraoka ◽  
Hidetaka Honda ◽  
Kota Nabeya ◽  
Kazushi Kinbara
Keyword(s):  
Polymeric Materials ◽  
Stimuli Responsive ◽  
Amphiphilic Molecules ◽  
Redox Responsive ◽  
Reversible Formation ◽  
Processing Control

A trifunctional amphiphile consisting of thermo-responsive, redox-responsive, and photo-responsive units achieved reversible formation of multiple stimuli-responsive polymeric materials.

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

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2714 ◽  
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.

scholarly journals Development of a New Hyaluronic Acid Based Redox-Responsive Nanohydrogel for the Encapsulation of Oncolytic Viruses for Cancer Immunotherapy

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 144
Author(s):  
Siyuan Deng ◽  
Alessandra Iscaro ◽  
Giorgia Zambito ◽  
Yimin Mijiti ◽  
Marco Minicucci ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Electron Microscope ◽  
Delivery System ◽  
Disulfide Bonds ◽  
Neutralizing Antibodies ◽  
Systemic Administration ◽  
Oncolytic Viruses ◽  
Host Immune System ◽  
Redox Responsive ◽  
The Stability

Oncolytic viruses (OVs) are emerging as promising and potential anti-cancer therapeutic agents, not only able to kill cancer cells directly by selective intracellular viral replication, but also to promote an immune response against tumor. Unfortunately, the bioavailability under systemic administration of OVs is limited because of undesired inactivation caused by host immune system and neutralizing antibodies in the bloodstream. To address this issue, a novel hyaluronic acid based redox responsive nanohydrogel was developed in this study as delivery system for OVs, with the aim to protect the OVs following systemic administration. The nanohydrogel was formulated by water in oil (W/O) nanoemulsion method and cross-linked by disulfide bonds derived from the thiol groups of synthesized thiolated hyaluronic acid. One DNA OV Ad[I/PPT-E1A] and one RNA OV Rigvir® ECHO-7 were encapsulated into the developed nanohydrogel, respectively, in view of their potential of immunovirotherapy to treat cancers. The nanohydrogels showed particle size of approximately 300–400 nm and negative zeta potential of around −13 mV by dynamic light scattering (DLS). A uniform spherical shape of the nanohydrogel was observed under the scanning electron microscope (SEM) and transmission electron microscope (TEM), especially, the successfully loading of OV into nanohydrogel was revealed by TEM. The crosslinking between the hyaluronic acid chains was confirmed by the appearance of new peak assigned to disulfide bond in Raman spectrum. Furthermore, the redox responsive ability of the nanohydrogel was determined by incubating the nanohydrogel into phosphate buffered saline (PBS) pH 7.4 with 10 μM or 10 mM glutathione at 37 °C which stimulate the normal physiological environment (extracellular) or reductive environment (intracellular or tumoral). The relative turbidity of the sample was real time monitored by DLS which indicated that the nanohydrogel could rapidly degrade within 10 h in the reductive environment due to the cleavage of disulfide bonds, while maintaining the stability in the normal physiological environment after 5 days. Additionally, in vitro cytotoxicity assays demonstrated a good oncolytic activity of OVs-loaded nanohydrogel against the specific cancer cell lines. Overall, the results indicated that the developed nanohydrogel is a delivery system appropriate for viral drugs, due to its hydrophilic and porous nature, and also thanks to its capacity to maintain the stability and activity of encapsulated viruses. Thus, nanohydrogel can be considered as a promising candidate carrier for systemic administration of oncolytic immunovirotherapy.

A redox-responsive drug delivery system based on RGD containing peptide-capped mesoporous silica nanoparticles

2015 ◽  
Vol 3 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Ze-Yong Li ◽  
Jing-Jing Hu ◽  
Qi Xu ◽  
Si Chen ◽  
Hui-Zhen Jia ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Drug Delivery System ◽  
Cellular Uptake ◽  
Delivery System ◽  
Disulfide Bonds ◽  
Mesoporous Silica Nanoparticles ◽  
Redox Responsive ◽  
Smart Drug ◽  
Smart Drug Delivery

A smart drug delivery system, DOX@MSN-S-S-RGD, was constructed by anchoring the RGD containing peptides onto the surface of MSNs using disulfide bonds for enhanced tumor cellular uptake and subsequent efficient cell killing.

PEGylated hyperbranched polyphosphoester based nanocarriers for redox-responsive delivery of doxorubicin

2016 ◽  
Vol 4 (3) ◽  
pp. 412-417 ◽  
Author(s):  
Chao Chen ◽  
Pan Zheng ◽  
Ziyang Cao ◽  
Yinchu Ma ◽  
Jie Li ◽  
...  
Keyword(s):  
Delivery System ◽  
Disulfide Bonds ◽  
System P ◽  
Redox Responsive

A PEGylated hyperbranched polyphosphoester containing multiple disulfide bonds (ss-hbPPE) was used and evaluated as a redox-responsive delivery system.

Tumor specific delivery with redox-triggered mesoporous silica nanoparticles inducing neovascularization suppression and vascular normalization

RSC Advances ◽  
2015 ◽  
Vol 5 (68) ◽  
pp. 55566-55578 ◽  
Author(s):  
Lu Sun ◽  
Yu-Jie Liu ◽  
Zhen-Zhen Yang ◽  
Xian-Rong Qi
Keyword(s):  
Gene Delivery ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Disulfide Bonds ◽  
Mesoporous Silica Nanoparticles ◽  
Vascular Normalization ◽  
Redox Responsive

Redox-responsive mesoporous silica nanoparticles with enlarged pores (denoted as MSN-siRNA/CrPEI) were designed by immobilizing polyethylenimine (PEI)viaintermediate linkers of disulfide bonds onto the MSNs as caps for redox-responsive intracellular gene delivery.

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