Biomaterials Science
·
2023
·Vol. 11
·期 10
·3709-3725
·
IF 6.6
Xiaofei Xin,Jingjing Li,Wantao Wu,Pengbo Zhao,Yang Yang,Ying Zhu,Lianjie Ren,Chao Qin,Lifang Yin
Non-alcoholic fatty liver disease (NAFLD) is a chronic inflammatory disease characterized by “multiple crosstalk” paths of insulin resistance, lipid metabolism, oxidative stress, etc. The combination of LY294002 and oridonin was proposed as a promising therapy by targeting insulin–PI3K/AKT signaling and NF-κB inflammatory pathway. However, due to oxidative stress, disease-associated upregulation of murine CYP3A11 activity can contribute to unexpected drug metabolism and disposition, which could seriously hinder the efficacy of LY294002 and oridonin. Nanotechnology-based effective reactive oxygen species (ROS) scavengers have emerged as a promising strategy to overcome these limitations. In this study, a rationally designed ROS-responsive liposome loaded with oridonin and LY294002 (RLLs) was developed for effective liver deposition and metabolic regulation for NAFLD treatment. First, we ascertained that the insulin resistance-induced signaling response was balanced by the combination of LY294002 and oridonin. Then, the particle size, zeta potential, ROS-responsive release behavior, and ROS-scavenging properties were investigated. Moreover, the CCl4-exposed mouse model was used to assess the biodistribution and therapeutic efficacy of RLLs on NAFLD. Finally, the “multiple crosstalk” modulation of RLLs was explored by western blotting, enzyme-linked immunosorbent assay, and polymerase chain reaction analysis. RLLs exhibited antioxidant efficacy for the safe delivery of LY294002 and oridonin with good stability and biocompatibility. The biodistribution analysis proved that the accumulation of RLLs was significantly increased due to CD44-mediated targeting. In addition, RLLs had comprehensive protective effects on the CCl4-exposed mouse model, leading to significant elimination of excessive ROS, maintenance of insulin sensitivity and CYP450 activity, and reduction of inflammatory response. In the CCl4-induced mice, RLL intervention remarkably improved metabolic profiles and reduced the fibrosis lesions. Our results provided a strategy for the amelioration of oxidative stress and CYP450 activity using ROS-responsive thioketal as an antioxidant adjuvant facilitated by nanotechnology.
研究领域:
药理学
·
纳米技术
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2019
·Vol. 108
·期 1
·148-156
·
IF 3.221
Yanli Bao,Liping Yin,Lin Liu,Li Chen
In order to improve the treatment efficacy and reduce the side effects, the synergistic therapy has been effectively exploited in cancer treatment. Herein, we fabricated a kind of acid-sensitive ROS-triggered dextran-based drug delivery system (DHTD/Zn-TPP) for synergistic therapy, in which chemotherapeutics doxorubicin was conjugated to the dextran backbone via ROS cleavable thioketal conjugates while photosensitizer porphyrin (Zn-TPP) was encapsulated via acid-responsive metallic coordinated interaction. The structure and acid-responsive self-assemble behavior of DHTD/Zn-TPP were measured by 1 H NMR, Fourier transform infrared, dynamic laser scattering, and transmission electron microscopy. Further, the in vivo ROS-triggered DOX release and anticancer efficiency were evaluated toward HeLa cells and MCF-7 cells. All the data obtained verified that DHTD/Zn-TPP had a significantly improved cell growth inhibitory effect with light irritation due to the combined application of photodynamic-chemotherapy.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2021
·
IF 11.556
Li Luo,Guangchao Zang,Boyan Liu,Xian Qin,Yuchan Zhang,Yidan Chen,Haijun Zhang,Wei Wu,Guixue Wang
Rationale: As a potentially life-threatening disorder, cerebral ischemia-reperfusion (I/R) injury is associated with significantly high mortality, especially the irreversible brain tissue damage associated with increased reactive oxygen radical production and excessive inflammation. Currently, the insufficiency of targeted drug delivery and “on-demand” drug release remain the greatest challenges for cerebral I/R injury therapy. Bioengineered cell membrane-based nanotherapeutics mimic and enhance natural membrane functions and represent a potentially promising approach, relying on selective interactions between receptors and chemokines and increase nanomedicine delivery efficiency into the target tissues. Methods: We employed a systematic method to synthesize biomimetic smart nanoparticles. The CXCR4-overexpressing primary mouse thoracic aorta endothelial cell (PMTAEC) membranes and RAPA@HOP were extruded through a 200 nm polycarbonate porous membrane using a mini-extruder to harvest the RAPA@BMHOP. The bioengineered CXCR4-overexpressing cell membrane-functionalized ROS-responsive nanotherapeutics, loaded with rapamycin (RAPA), were fabricated to enhance the targeted delivery to lesions with pathological overexpression of SDF-1. Results: RAPA@BMHOP exhibited a three-fold higher rate of target delivery efficacy via the CXCR4/SDF-1 axis than its non-targeting counterpart in an in vivo model. Additionally, in response to the excessive pathological ROS, nanotherapeutics could be degraded to promote “on-demand” cargo release and balance the ROS level by p -hydroxy-benzyl alcohol degradation, thereby scavenging excessive ROS and suppressing the free radical-induced focal damage and local inflammation. Also, the stealth effect of cell membrane coating functionalization on the surface resulted in extended circulation time and high stability of nanoparticles. Conclusion: The biomimetic smart nanotherapeutics with active targeting, developed in this study, significantly improved the therapeutic efficacy and biosafety profiles. Thus, these nanoparticles could be a candidate for efficient therapy of cerebral I/R injury.
研究领域:
纳米医学
·
药学
·
神经科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 6
·5156-5165
·
IF 4.171
Yu-Sheng Shi,Xiao-Xing Li,Hao-Tian Li,Yan Zhang
Liver fibrosis is a histological change that often occurs due to hepatic stellate cell (HSC) activation and excessive formation of an extracellular matrix in the liver. Pelargonidin (PEL) is a natural anthocyanidin existing in blueberries, berries, strawberries, and red radishes and has been demonstrated to possess health beneficial effects. Herein, we investigated the effect of PEL on liver fibrosis induced by CCl4 and hepatic stellate cells induced by transforming growth factor-β (TGF-β). We found that PEL administration prevented liver injury and liver fibrosis induced by CCl4 in a dose-dependent manner. Further data revealed that PEL increased liver nuclear factor E2-related factor 2 (Nrf2) and reduced liver oxidative stress and the expression levels of NLRP3, caspase-1 and IL-1β. In TGF-β-challenged HSCs (LX-2 cells), PEL effectively inhibited the LX-2 cell activation. In addition, the anti-fibrosis effects of PEL in LX-2 cells were abolished by Nrf2 knockdown. In summary, our study demonstrated that PEL ameliorated CCl4-induced liver fibrosis and HSC activation induced by TGF-β. The possible molecular mechanisms of PEL in liver fibrosis may be attributed to its suppression of ROS-NLRP3-IL-1β signaling by Nrf2 activation.
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Meizhe Yu,Gaoke Zhang,Peili Li,Haojie Lu,Wentao Tang,Xu Yang,Ruobing Huang,Fan Yu,Wenzhen Wu,Yuhong Xiao,Xiaodong Xing
Many medical and chemical applications require the precise supply of antimicrobial components in a controlled manner at the location of mature biofilm deposits. This work reports a facile strategy to fabricate nanoscale metal-organic frameworks (NMOFs) coencapsulating the antibacterial ligand (lysine carbon dots, Lys-CDs) and targeted drug (folic acid, FA) in one pot to improve antibiofilm efficiency against established biofilms. The resulting products are characterized by transmission electron microscopy, field-emission scanning electron microscopy, powder x-ray diffraction, and ultraviolet-visible spectroscopy. The results show that Lys-CDs could coordinate with Zn 2+ and the adding of FA inhibits the coordination of Lys-CDs with central ions of Zn. The Lys-CDs and FA are successfully exposed with the NMOFs disintegrating in the acid environment of bacterial metabolites. We are surprised to find a sharp increase of reactive oxygen species (ROS) inside the bacterial cells by FA functionalizing NMOFs, which undoubtedly enhance the antibacterial and antibiofilm activity. The as-synthesized ZIF-8-based nanocomposites also show the peroxidase-like activity in an acid environment, and produce extremely active hydroxyl radicals resulting in the improved antibacterial and antibiofilm activity. The possible mechanisms of antibacterial activities indicate that the presence of FA is significant in the sense of targeting bacteria. This study shows a novel approach to construct acid stimulation supply system which may be helpful for the research of antibiofilms.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 40
·期 9
·1101-1109
·
IF 3.815
Li Yu-Tong,Sheng Si-Ting,Yu Bo,Jia Fan,Wang Kai,Han Hai-Jie,Jin Qiao,Wang You-Xiang,Ji Jian
Uveitis is a sophisticated syndrome showing a high relevance with reactive oxygen species (ROS). Herein, an ROS-responsive PEGylated polypeptide based macromolecular prodrug of herbaceous antioxidant ethyl caffeate (EC) is designed via phenylboronic esters with improved solubility for the alleviation of uveitis. The antioxidative 4-hydroxybenzyl alcohol (HBA) and EC can be released from the macromolecular EC prodrug under the stimulation of ROS, which can effectively protect cells against oxidative stress-induced injury in an ROS-depletion way. The antioxidative and protective effects of the macromolecular EC prodrug in vivo are further verified in a uveitis mouse model. Overall, this work not only provides a handy method to synthesize a phenylboronic ester-bearing EC prodrug which is highly sensitive to pathological ROS, but also depicts a promising future to apply macromolecular antioxidative prodrugs in the treatment of uveitis as well as other ROS-related diseases.
研究领域:
药学
·
眼科学
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 7
·936
·
IF 4.9
Peng Chen,Zhihui Wang,Xinmo Wang,Junni Gong,Ju Sheng,Yufei Pan,Dandan Zhu,Xiaoxuan Liu
Small interfering RNA (siRNA) therapeutics, characterized by high specificity, potency, and durability, hold great promise in the treatment of cancer and other diseases. However, the clinic implementation of siRNA therapeutics critically depends on the safe and on–demand delivery of siRNA to the target cells. Here, we reported a family of ferrocenyl amphiphilic dendrimers (Fc-AmDs) for on–demand delivery of siRNA in response to the high ROS content in cancer cells. These dendrimers bear ROS–sensitive ferrocene moieties in the hydrophobic components and positively chargeable poly(amidoamine) dendrons as the hydrophilic entities, possessing favorable safety profiles and ROS responsive properties. One of these ferrocenyl amphiphilic dendrimers,Fc-C8-AmD 8A, outperforms in siRNA delivery, benefiting from its optimal balance of hydrophobicity and hydrophilicity. Its ROS feature facilitates specific and efficient disassembly of its complex with siRNA in ROS–rich cancer cells for effective siRNA delivery and gene silencing. Moreover,Fc-C8-AmD 8Aalso integrates the features and beneficial properties of both lipid and dendrimer vectors. Therefore, it represents a novel on–demand delivery system for cancer cell–specific siRNA delivery. This work opens new perspectives for designing self–assembly nanosystems for on–demand drug delivery.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 8
·5577-5587
·
IF 3.9
Kai Li,Sinan Tian,Ke Sun,Qingguo Su,Yanhui Mei,Wenjie Niu
Prostate cancer is the most common malignant tumor in the male reproductive system, and its incidence increases with age. Chemotherapy is one of the main strategies for treating prostate cancer, but it often comes with unavoidable side effects. Nanocarriers can improve drug utilization and targeting, and cationic carriers can also carry nucleic acids for gene therapy. In this study, we prepared a cationic micelle constructed from a polyprodrug that can deliver both chemotherapeutic drugs and nucleic acids simultaneously. The typical chemotherapeutic drug hydroxycamptothecin (HCPT) was linked by reactive oxygen species (ROS)-responsive coupling agents and forms amphiphilic block polymers with low molecular weight polyethyleneimine (PEI). The resulting cationic micelles can be triggered by high levels of ROS in tumor cells and collapse to release HCPT and suicide genes to kill tumor cells. At the same time, it reduces the killing of normal cells. In prostate cancer cells, it has been confirmed that the co-delivery carriers combined with chemotherapy and a suicide gene prodrug system have shown an ideal therapeutic effect on prostate cancer.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Zhanhao Zhou,Hongbing Lan,Hongyuan Tan,Yi Wang,Wei Chen,Samira Batur,Chuansheng Fu,Li Kong,Conglian Yang,Boning Niu,Yuanyuan Guo,Zhiping Zhang,Kai Huang
Atherosclerosis, characterized by the accumulation of inflammatory cells at localised inflammatory sites with a high concentration of reactive oxygen species (ROS), is a leading cause of cardiovascular morbidity and mortality worldwide. There is a paucity of studies that effectively coordinate the targeting of inflammatory microenvironment and the controlled release of biomimetic carriers. Here, in view of the oxidative stress and inflammatory characteristics observed in the plaque microenvironment of atherosclerosis lesions, we propose an anti-inflammatory M2 macrophage membrane-derived nanovesicles co-fused with lipids containing ROS-sensitive thioketal (TK) linker and loaded with rapamycin (Rapa) to form a biomimetic hybrid system (Rapa@TLNVs). Benefiting from the inflammatory tendency of vesicles and ROS response of TK, Rapa@TLNVs can be delivered to plaque lesions and responsively release Rapa to synergistically help suppressing inflammation. Additionally, Rapa@TLNVs can reduce foam cells formation and the proliferation of macrophages. Following the administration of Rapa@TLNVs to ApoE −/− mice, a series of effects have been observed, including reductions in the inflammatory response, lipid deposition and increased plaque stability. Consequently, this work exploits the characteristics of the atherosclerosis plaque microenvironment to provide a promising strategy for combating atherosclerosis. This may further enrich the application experience of biomimetic hybrid nanovesicle platforms in atherosclerosis therapy.
研究领域:
心血管疾病
·
纳米技术
·
药学
·
炎症
✓ 已验证
产品关联
DOI
高影响因子
Bosnian Journal of Basic Medical Sciences
·
2022
·
IF 3.759
Peng Hua,Donglin Yang,Ruie Chen,Peiqi Qiu,Meiwan Chen
Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity, while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF 12.5%, TKPF 25%, and TKPF 50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Fluorination reduced the positive charge density and endowed hydrophobic and lipophobic characteristics to resist serum interactions. The fluorophilic effect mediated efficient cellular uptake and endosomal escape while ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. TKPFs also exhibited great serum resistance in gene delivery and TKPF 50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrate that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.
研究领域:
生物医学工程
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Zhang Liding,Cao Kai,Xie Jun,Liang Xiaohan,Gong Hui,Luo Qingming,Luo Haiming
Amyloid-β (Aβ) readily misfolds into neurotoxic aggregates, generating high levels of reactive oxygen species (ROS), leading to progressive oxidative damage and ultimately cell death. Therefore, simultaneous inhibition of Aβ aggregation and scavenging of ROS may be a promising therapeutic strategy to alleviate Alzheimer’s disease pathology. Based on the previously developed antibody 1F12 that targets all forms of Aβ 42 , we developed an Aβ 42 and ROS dual-targeting nanocomposite using biodegradable mesoporous silica nanoparticles as carriers to load ultra-small cerium oxide nanocrystals (bMSNs@Ce-1F12). By modifying the brain-targeted rabies virus glycoprotein 29 (RVG29-bMSNs@Ce-1F12), this intelligent nanocomposite can efficiently target brain Aβ-rich regions. Combined with peripheral and central nervous system treatments, RVG29-bMSNs@Ce-1F12 can significantly alleviate AD symptoms by inhibiting Aβ 42 misfolding, accelerating Aβ 42 clearance, and scavenging ROS. Furthermore, this synergistic effect of ROS scavenging and Aβ clearance exhibited by this Aβ 42 and ROS dual-targeted strategy also reduced the burden of hyperphosphorylated tau, alleviated glial cell activation, and ultimately improved cognitive function in APP/PS1 mice. Our findings indicate that RVG29-bMSNs@Ce-1F12 is a promising nanodrug that can facilitate multi-target treatment of AD.
研究领域:
神经科学
·
纳米技术
·
药学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Select
·
2022
·Vol. 3
·期 11
·1537-1547
·
IF 0
Wenshuai Liu,Litao Jia,Sichun Zhao,Yue Ma,Siyu Liu,Qian Wang,Xiaoyan Lv,Haiyue Jiang,Xia Liu
Bacterial infection can cause delay in wound healing, and reactive oxygen species (ROS) was accumulated in wounds, which threaten patients’ lives. Therefore, it needs to develop a multifunctional hydrogel for infected wound healing. Here, a multifunctional QAS-CS@GA-GM hydrogel with antibacterial and antioxidant property, established by the self-adaptive covalent bond, is prepared aiming to eradicate bacteria and eliminate ROS. It is observed that QAS-CS@GA-GM hydrogel displays remarkable ability of clearing ROS and killing bacteria in vitro. With its antibacterial and antioxidant activity, QAS-CS@GA-GM hydrogel significantly accelerates the MRSA-infected wound closure and reduces inflammatory, when QAS-CS@GA-GM hydrogel was applied to wound sites. Collectively, the research suggests that a self-adaptive QAS-CS@GA-GM hydrogel is a promising wound dressing as antibacterial and ROS-scavenging dressing for bacterial-infected wound.
研究领域:
生物材料
·
伤口敷料
·
抗氧化
·
抗感染
✓ 已验证
DOI
危险品化学品经营许可证（带存储）