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.

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.

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

A bio-inspired fluorescent nano-injectable hydrogel as a synergistic drug delivery system

2021 ◽  
Vol 45 (6) ◽  
pp. 3079-3087
Author(s):  
Yue Xu ◽  
Mingming Yang ◽  
Qiyue Ma ◽  
Xiang Di ◽  
Guolin Wu
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Fluorescence Properties ◽  
Injectable Hydrogel ◽  
Sequential Release ◽  
System P

A nano-injectable hydrogel with fluorescence properties and controlled sequential release of dual drugs.

Phenylboronic acid-functionalized polyaminoglycoside as an effective CRISPR/Cas9 delivery system

2021 ◽  
Author(s):  
Meiyu Shao ◽  
Yu Qi ◽  
Dandan Sui ◽  
Fu-Jian Xu
Keyword(s):  
Delivery System ◽  
Tumor Targeting ◽  
Phenylboronic Acid ◽  
System P

One tumor-targeting, phenylboronic acid-functionalized polyaminoglycoside (SS-HPT-P) was proposed as a safe and effective CRISPR/Cas9 delivery system for the treatment of carcinoma.

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.

Distinct photophysical behaviour and transport of cell-impermeable [Ru(bpy)2dppz]2+ in live cells using cucurbit[7]uril as a delivery system

2018 ◽  
Vol 47 (11) ◽  
pp. 3857-3863 ◽  
Author(s):  
Meenakshi N. Shinde ◽  
Soniya S. Rao ◽  
Shridhar P. Gejji ◽  
Anupa A. Kumbhar
Keyword(s):  
Cell Membrane ◽  
Delivery System ◽  
Live Cells ◽  
System P ◽  
Molecular Container ◽  
A Cell

We have successfully demonstrated the delivery of a cell-impermeable [Ru(bpy)2dppz]2+ complex across the cell membrane in live cells using a cucurbit[7]uril molecular container.

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 Development and in vitro Evaluation of Gastro-protective Aceclofenac-loaded Self-emulsifying Drug Delivery System

2020 ◽  
Vol Volume 15 ◽  
pp. 5217-5226 ◽  
Author(s):  
Chen Jianxian ◽  
Kalsoom Saleem ◽  
Muhammad Ijaz ◽  
Masood Ur-Rehman ◽  
Ghulam Murtaza ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
In Vitro Evaluation ◽  
System P

scholarly journals Echogenic PEGylated PEI-Loaded Microbubble As Efficient Gene Delivery System

2019 ◽  
Vol Volume 14 ◽  
pp. 8923-8941 ◽  
Author(s):  
Chun Liufu ◽  
Yue Li ◽  
Jiawei Tu ◽  
Hui Zhang ◽  
Jinsui Yu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Gene Delivery System ◽  
System P ◽  
Efficient Gene
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