COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Xian Guo,Borui Zhang,Yutong Chen,Zhi Jia,Xiaoyu Yuan,Li Zhang,Jie Liu,Yanan Liu
Clinical trials based on a single molecular target continue to fail, and the adverse effects of Aβ protein aggregation and neuroinflammation need to be solved and treatment of Alzheimer's disease. Herein, by designed a nano-sized flower mesoporous selenium transport carrier (Met@MSe@Tf) with high enzyme-like activity, metformin (Met) was loaded, and transferrin (Tf) was modified to bind to transferrin receptor to promote receptor-mediated transport across the BBB. In the AD lesion environment, with the acidic environment response dissociation, promote the release of metformin by nanoflower to achieve therapeutic effect in the brain lesion site. Metformin, a major anti-diabetic drug in diabetic metabolism, has been found to be a promising new therapeutic target in neurodegenerative diseases. Further studies showed that the metformin drug release from the designed and synthesized transport nanoparticles showed high intrinsic activity and the ability to degrade the substrate involved, especially the degradation of Aβ deposition in the cortex and hippocampus, increased the phagocytosis of microglia, thus relieving neuroinflammation simultaneously. Collectively, in vivo experiments demonstrated that Met@MSe@Tf significantly increased the number of NeuN-positive neurons in the hippocampus of AD mice, promoted neurovascular normalization in the brain, and improved cognitive dysfunction in AD transgenic AD mice. Thus, it provides a preclinical proof of concept for the construction of a highly modular accurate drug delivery platform for Alzheimer's disease.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Ronggang Liu,Xiumin Zhang,Siyuan Fei,Mingqian Tan
The excessive production of reactive oxygen species (ROS) inside mitochondria is a significant factor in the perpetuation of dry eye disease (DED), and it may be a key target for DED treatment. In this work, we designed and prepared orally deliverable lutein nanoparticles formulated with phycocyanin, chitosan modified with triphenylphosphonium (TPP), and yeast β-glucan modified with 3-boronobenzoic acid. These nanoparticles possess dual-targeting abilities for microfold cells in Peyer’s patches and ocular cell mitochondria to intervene in DED. Our data demonstrated that the dual-targeted lutein nanoparticles effectively accumulated within Peyer’s patches and were endocytosed by resident immune cells. In vitro results demonstrated that dual-targeted lutein nanoparticles showed excellent mitochondrial targeting ability with a Pearson correlation value of 0.86 after incubation for 4 h. In vivo results showed that the accumulation of lutein in mouse eye mitochondria increased by 2.36 times. Furthermore, the dual-targeted lutein nanoparticles alleviated oxidative stress damage of the cornea by reducing ROS levels in the cornea, and reduced corneal inflammation and keratinization, thus alleviating DED. The novel lutein nanoparticles with dual abilities to improve absorption efficiency and target mitochondria can be used as a promising candidate for oral intervention in DED.
✓ 已验证
产品关联
DOI
高影响因子
Matter
·
2025
·
IF 17.5
Shang Chi,Yaping Li,Tingting Ye,Jiawei Kang,Zhihui Xiang,Xiaoqing Kuang,Chenggang Yi,Yiying Qi,Wei Wang
This work developed a de novo sonosensitizer based on carnosine_zinc piezoelectric metal-organic frameworks (PMOFs) that possesses a prominent reactive oxygen species (ROS)-generating function, biocompatibility, and degradability. Further, the PMOF was modified by a carbon monoxide (CO) donor through a metal complexation reaction to result in a multifunctional CO-PMOF to launch CO/ROS-mediated antimicrobial under ultrasound (US). However, the heat generated during sonodynamic therapy (SDT) may harm wounds. To minimize the waste energy and promote wound self-closure rate, a strong adhesive, and rapid thermal-responsive contraction (52.4%, 4 min), injectable hydrogel was designed to load CO-PMOF. The resulting ultrasonic triple-responsive hydrogel (UTGel) exhibits an effective biofilm destruction capability based on a CO/ROS-mediated antimicrobial therapy. After administration in an infected diabetic skin wound model in mice, UTGel can efficiently harvest the thermal energy by the CO-PMOF under US to trigger a centripetal shrinkage of the hydrogel and guide rapid wound self-closure.
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Wenjing Yang,Chenhang Ding,Yibing Ji,Chongxian He,Feilong Xiong,Wurikaixi Aiyiti,Cijun Shuai
The overexpression of glutathione (GSH) within the tumor microenvironment has long been considered as the major obstacle for reactive oxygen species (ROS)-based antitumor therapies. To address this challenge, a selenite (SeO 3 2 − ) and ferric ion co-doped hydroxyapatite (SF-HAP) nanohybrid was synthesized, which is then introduced into poly-L-lactic acid (PLLA) to prepare porous scaffold by selective laser sintering to continuously release Fe 3+ and SeO 3 2− ions. Of great significance is the released SeO 3 2− catabolize GSH to generate superoxide anion (O 2 •− ) rather than directly eliminating GSH, thereby reversing the obstacle posed by its overexpression and achieving a "waste-to-treasure" transformation. The newly generated O 2 •− synergizes with the hydroxyl radicals (•OH) produced by the Fenton reaction between Fe 3+/2+ and hydrogen peroxide, triggering high concentration ROS storms. Collectively, the PLLA/SF-HAP scaffold mediated self-augmented catabolism dynamic progress significantly raised intracellular ROS levels, almost twice as much as PLLA/Fe-HAP scaffold, thereby effectively inducing tumor cell apoptosis. The study provides an innovative inspiration for ROS-based antitumor therapies.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2024
·
IF 3.3
Xiaomeng Ji,Jiajia Guo,Yeyun Ma,Shuai Zhang,Zuwang Yang,Yuanyuan Li,Kaixin Ping,Yue Xin,Zibo Dong
Difenoconazole (DFZ) is a fungicidal pesticide extensively employed for the management of fungal diseases in fruits, vegetables, and cereal crops. However, its potential environmental impact cannot be ignored, as DFZ accumulation is able to lead to aquatic environment pollution and harm to non-target organisms. Quercetin (QUE), a flavonoid abundant in fruits and vegetables, possesses antioxidant and anti-inflammatory properties. In this article, carp were exposed to 400 mg/kg QUE and/or 0.3906 mg/L DFZ for 30 d to investigate the effect of QUE on DFZ-induced respiratory toxicity in carp. Research shows that DFZ exposure increases reactive oxygen species (ROS) production in the carp's respiratory system, leading to oxidative stress, inflammation, and damage to gill tissue and tight junction proteins. Further research demonstrates that DFZ induces mitochondrial dynamic imbalance and gill cell apoptosis. Notably, QUE treatment significantly reduces ROS levels, alleviates oxidative stress and inflammation, and mitigates mitochondrial dynamics imbalance and mitochondrial apoptosis. This study emphasizes the profound mechanism of DFZ toxicity to the respiratory system of common carp and the beneficial role of QUE in mitigating DFZ toxicity. These findings contribute to a better understanding of pesticide risk assessment in aquatic systems and provide new insights into strategies to reduce their toxicity.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Yu Shi,Wenzhen Bu,Dongchuan Chu,Wenzheng Lin,Ke Li,Xueping Huang,Xinglong Wang,Yin Wu,Shang Wu,Dandan Li,Zhuobin Xu,Zhipeng Cao,Hao Chen,Huihui Wang
Intervertebral disc degeneration (IVDD) is invariably accompanied by excessive accumulation of reactive oxygen species (ROS), resulting in progressive deterioration of mitochondrial function and senescence in nucleus pulposus cells (NPCs). Significantly, the main ROS production site in non-immune cells is mitochondria, suggesting mitochondria is a feasible therapeutic target to reverse IVDD. Triphenylphosphine (TPP), which is known as mitochondrial-tropic ligands, is utilized to modify carbon dot-supported Prussian blue (CD-PB) to scavenge superfluous intro-cellular ROS and maintain NPCs at normal redox levels. CD-PB-TPP can effectively escape from lysosomal phagocytosis, permitting efficient mitochondrial targeting. After strikingly lessening the ROS in mitochondria via exerting antioxidant enzyme-like activities, such as superoxide dismutase, and catalase, CD-PB-TPP rescues damaged mitochondrial function and NPCs from senescence, catabolism, and inflammatory reaction in vitro. Imaging evaluation and tissue morphology assessment in vivo suggest that disc height index, mean grey values of nucleus pulposus tissue, and histological morphology are significantly improved in the IVDD model after CD-PB-TPP is locally performed. In conclusion, this study demonstrates that ROS-induced mitochondrial dysfunction and senescence of NPCs leads to IVDD and the CD-PB-TPP possesses enormous potential to rescue this pathological process through efficient removal of ROS via targeting mitochondria, supplying a neoteric strategy for IVDD treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Junlin Chen,Qingtao Li,Chuhan Lv,Hongbo Yu,Cheng Dai,Ye Hu,Hua Dong
Articular cartilage repair remains challenging due to the inherent poor self-healing capacity and acute inflammation resulting from the over expression of intracellular reactive oxygen species (ROS). Although microfracture is frequently used in practical surgery, the newborn cartilage always exhibits fibrosis, mainly attributed to the weak ROS scavenging and mismatched microenvironment that fails to induce chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Herein, a novel simvastatin (SIM)-incorporated kelp and cartilage acellular matrix hybrid (labeled as SIM@KACM/CACM) microgel assembly with enhanced ROS scavenging, endogenous BMSC recruitment, and chondrogenic differentiation capabilities is constructed to improve microfracture-based articular cartilage repair. The kelp acellular matrix exhibits low immunogenicity, high biocompatibility, and ROS scavenging properties, whilst the sustained SIM release promotes BMSC recruitment from the bone marrow cavity. Meanwhile, the microenvironment and bioactive factors conferred by CACM facilitate the BMSC proliferation and differentiation into hyaline cartilage. In addition, the construction of porous microgel assembly via dynamic Schiff's bonds endows excellent injectability and tissue adhesion, which not only enhances its retention in the defect site after injection but also provides abundant sites for BMSC anchoring and infiltration. Due to the synergetic effect of the above-mentioned multiple factors, the articular cartilage repair is improved dramatically.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale Advances
·
2020
·Vol. 2
·期 9
·3872-3881
·
IF 0
Yihuan Liu,Haibin Liu,Li Wang,Yingjie Wang,Chengcheng Zhang,Changping Wang,Yang Yan,Jingpin Fan,Guanghui Xu,Qiang Zhang
Cancer cells are commonly characterized by high cellular oxidative stress and thus have poor tolerance to oxidative insults. In this study, we developed a nano-formulation to elevate the level of reactive oxygen species (ROS) in cancer cells via promoting ROS production as well as weakening cellular anti-oxidizing systems. The nanoagent was fabricated by encapsulating two natural product molecules, cinnamaldehyde (CA) and diallyl trisulfide (DATS), in PLGA–PEG copolymer formulated nanoparticles. CA promotes ROS generation in cancer cells and DATS depletes cellular glutathione. CA and DATS exhibited a synergistic effect in amplifying the ROS levels in cancer cells and further in their combined killing of cancer cells. The in vivo experiments revealed that the CA and DATS-encapsulated nanoagent suppressed tumors more efficiently as compared with the single drug-loaded ones, and the tumor-targeted delivery further enhanced the therapeutic efficacy. This study suggests that the combined enhancement of oxidative stress by CA and DATS could be a promising strategy for cancer therapy.
✓ 已验证
DOI
PubMed
Acta Biomaterialia
·
2022
·
IF 10.633
Rong Shi,Haisheng Li,Xin Jin,Xue Huang,Zelin Ou,Xuanfen Zhang,Gaoxing Luo,Jun Deng
Engineering smart nano-therapeutics for re-epithelialisation of chronic wounds facilitates the wound healing process. However, due to excessive oxidative stress damage and persistent inflammation in diabetic wound microenvironment, the migration of stimulating epidermal cells in diabetic wounds represents a significant challenge. Here we synthesised P311-loaded micelles by self-assembly of P311 peptides and diblock copolymer poly (ethylene glycol)-block-poly (propylene sulfide) (PEG-b-PPS, denoted as PEPS) that have unique ability to transform an oxidative wound microenvironment into a proregenerative one while also providing cues for epidermal cell migration. The [email protected] showed an accelerated migration of epidermal cells via activation of the Akt signalling pathway , simultaneously suppressing the unfavourable oxidative wound microenvironment by scavenging reactive oxygen species (ROS), ultimately leading to the induction of an environment conducive to cell migration. Furthermore, the micelles were able to bypass the inhibitory effect of ROS on the Akt signalling pathway, thereby promoting epidermal cell migration. Additionally, we observed that diabetic wounds treated with [email protected] showed accelerated chronic wound healing, granulation tissue formation, collagen deposition and re-epithelialisation, thereby suggesting the efficacy of [email protected] as a promising nanoplatform for the treatment of chronic wounds. Statement of significance Based on the unique conditions of the diabetic wound microenvironment, a smart drug delivery system with ROS-responsive nanomaterials has been widely investigated to enhance diabetic wound healing. In our previous studies, we observed that P311 promotes epidermal cell migration to induce wound re-epithelialisation. However, the application of P311 suffers from its instability. Herein, we developed a therapeutic platform with P311-loaded micelles ( [email protected] ), which were synthesized by the self-assembly of P311 peptides and diblock copolymer poly (ethylene glycol)-block-poly (propylene sulfide) (PEG-b-PPS, denoted as PEPS). These micelles provide continuous migration signals for epidermal cells by ROS-trigged P311 release. Additionally, [email protected] scavenges excess ROS and provides a microenvironment that reduces inflammation, which could protect P311 from enzymatic degradation and improve the bioavailability of P311.
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Zeqian Huang,Yanjuan Huang,Meixu Chen,Jie Chen,Zishan Zeng,Xiaoyu Xu,Binyao Huang,Yong Luo,Zhanghong Xiao,Yaqing Ding,Chunshun Zhao
The treatment of bone metastases remains an enormous challenge in clinical application. Strategies utilizing reactive oxygen species (ROS) to induce cell death show great potential for enhanced cancer therapy. Thus, for the first time, a versatile alendronate (ALN)-functionalized and cinnamaldehyde (CA)-loaded nanoscale coordination polymer (denoted as CA/ [email protected] ) based on 1,1′-ferrocenedicarboxylicacid (Fc) and L-buthionine-sulfoximine (BSO) was properly fabricated as an oxidative stress nanoamplifier for synergetic chemo/chemodynamic therapy of bone metastases. With appropriate size and strong bone affinity of ALN, CA/ [email protected] can preferentially accumulate in the bone metastatic site. In this nanoamplifier, CA can act as the ROS generator to produce ROS to damage cancer cells and boost intracellular hydrogen peroxide (H 2 O 2 ) level, which can be converted into hydroxyl radical (•OH) with the catalysis of Fc via Fenton reaction. Simultaneously, glutathione (GSH) depletion mediated by BSO can inhibit ROS elimination to maintain H 2 O 2 level and •OH amount, ultimately leading to superior antitumor effect. Both in vitro and in vivo results demonstrated the self-enhanced synergetic chemo/chemodynamic therapy of CA/ [email protected] Such a nanoamplifier can generate and maintain sufficient ROS without the introduced external light triggering, exactly addressing the dilemma posed by fewer light penetration as well as the uncertain location of bone metastases. This study not only provides a novel strategy to achieve excellent cancer therapy by boosting ROS generation and simultaneously inhibiting ROS elimination, but also creates the precedent for the application of chemodynamic therapy for bone metastases treatment.
✓ 已验证
DOI
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Dun Liu,Geng Lu,Bo Shi,Huanyu Ni,Jun Wang,Yong Qiu,Lin Yang,Zezhang Zhu,Xuan Yi,Xiao Du,Benlong Shi
Although stem cell-based therapy is recognized as a promising therapeutic strategy for spinal cord injury (SCI), its efficacy is greatly limited by local reactive oxygen species (ROS)-abundant and hyper-inflammatory microenvironments. It is still a challenge to develop bioactive scaffolds with outstanding antioxidant capacity for neural stem cells (NSCs) transplantation. In this study, albumin biomimetic cerium oxide nanoparticles (CeO 2 @BSA nanoparticles, CeNPs) are prepared in a simple and efficient manner and dispersed in gelatin methacryloyl to obtain the ROS-scavenging hydrogel (CeNP-Gel). CeNP-Gel synergistically promotes neurogenesis via alleviating oxidative stress microenvironments and improving the viability of encapsulated NSCs. More interestingly, in the presence of CeNP-Gel, microglial polarization to anti-inflammatory M2 subtype are obviously facilitated, which is further verified to be associated with phosphoinositide 3-kinase/protein kinase B pathway activation. Additionally, the injectable ROS-scavenging hydrogel is confirmed to induce the integration and neural differentiation of transplanted NSCs. Compared with the blank-gel group, the survival rate of NSCs in CeNP-Gel group is about 3.5 times higher, and the neural differentiation efficiency is about 2.1 times higher. Therefore, the NSCs-laden ROS-scavenging hydrogel represents a comprehensive strategy with great application prospect for the treatment of SCI through comprehensively modulating the adverse microenvironment.
✓ 已验证
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2017
·
IF 4.593
Shimei Qi,Zunyong Feng,Qiang Li,Zhilin Qi,Yao Zhang
Myricitrin, a naturally occurring polyphenol hydroxy flavonoid, has been reported to possess anti-inflammatory properties. However, the precise molecular mechanism of myricitrin’s effects on LPS-induced inflammation is unclear. In the present study, myricitrin significantly alleviated acute lung injury in mice. Myricitrin also markedly suppressed the production of NO, TNF-α, IL-6, and MCP-1 in RAW264.7 macrophage cells. The inhibition of NO was concomitant with a decrease in the protein and mRNA levels of iNOS. The phosphorylation of JAKs and STAT-1 was abrogated by myricitrin. Furthermore, myricitrin inhibited the nuclear transfer and DNA binding activity of STAT1. The JAK-specific inhibitor ruxolitinib simulated the anti-inflammatory effect of myricitrin. However, myricitrin had no impact on the MAPK signalling pathway. Myricitrin attenuated the generation of intracellular ROS by inhibiting the assembly of components of the gp91phox and p47phox. Suppression of ROS generation using NAC or apocynin or by silencing gp91phox and p47phox all demonstrated that decreasing the level of ROS inhibited the LPS-induced inflammatory response. Collectively, these results confirmed that myricitrin exhibited anti-inflammatory activity by blocking the activation of JAKs and the downstream transcription factor STAT1, which may result from the downregulation of NOX2-dependent ROS production mediated by myricitrin.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）