NEW JOURNAL OF CHEMISTRY
·
2024
·
IF 2.7
Xiaoyi Song,Fan Yang,Ruixuan Ji,Bin Yang,Yin Lv,Zhong Wei
Traditional chemotherapy faces challenges related to limited drug efficacy and adverse reactions. Intelligent nanocarrier drug delivery systems (INDDSs) promise improved treatment outcomes with reduced toxicity. However, several clinical challenges persist in achieving rapid drug release and real-time monitoring. Herein, a ROS-responsive amphiphilic copolymer was synthesized: polyethylene glycol (mPEG-TK-OH) with ROS-responsive thioketal (TK) as the macromolecular initiator, and enzymatic ring-opening polymerization of caprolactone was performed. Small molecules of tetraphenylethylene (TPE) with aggregation-induced emission (AIE) properties were added to the polymer's terminus to enable fluorescence imaging and the ROS-responsive amphiphilic copolymer mPEG-TK-PCL-TPE with AIE properties is formed and enhances drug release monitoring through fluorescence resonance energy transfer (FRET) between TPE and the hydrophobic anti-cancer drug DOX. Leveraging distinct ROS levels between tumor and normal cells, these ROS-responsive nanomicelles effectively respond to high intracellular redox-active species and release DOX. The mPEG-TK-PCL-TPE micelles displayed a suitable size, high drug loading, and excellent imaging quality. In vitro cell experiments confirmed their biocompatibility and efficacy in inhibiting 4T1 tumor cells. This ROS-responsive amphiphilic copolymer, incorporating the AIE structure, introduces new opportunities for cancer treatment, enabling real-time drug release tracking and improving therapeutic outcomes.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 16
·9260-9269
·
IF 3.049
Bin Yang,Kaiyuan Wang,Dong Zhang,Bin Ji,Dongyang Zhao,Xin Wang,Haotian Zhang,Qiming Kan,Zhonggui He,Jin Sun
Development of smart stimuli-responsive prodrug nanomaterials for fast drug release and efficient antitumor therapy has attracted great attention in recent years. However, the inherent instability of naked prodrugs in the blood is an important challenge limiting their biomedical applications. Although a number of strategies have been taken to prevent prodrugs from hydrolyzing due to blood composition, most of these strategies are unsatisfactory. Here, we designed an extraordinary ROS-triggered prodrug nanoplatform fabricated by using a single thioether linker to conjugate PTX with 6-maleimidocaproic acid (MAL), resulting in the PTX-S-MAL prodrug self-assembling into uniform size nanoparticles; then the prodrug nanoplatform was modified with a polydopamine coating and PEGylation to confer high solubility and stability. In in vitro experiments, the polydopamine-modified ROS-responsive prodrug nanosystem showed a high sensitivity in term of various H2O2 concentrations, and the PDA coating on the surface of the prodrug nanosystem didn't affect the drug release properties. Moreover, the excellent polydopamine-modified ROS-triggered prodrug nanoplatform selectively and rapidly releases PTX in response to the ROS overproduced in tumor cells, but showed less cytotoxicity against normal cells. In in vivo experiments, the prepared polydopamine-modified prodrug-nanosystem obviously enhances the stability and tumor accumulation of prodrug, producing a remarkably improved breast cancer treatment with minimal side effects. Our studies demonstrated that this modified nanoplatform could significantly improve chemotherapy efficiency, which will find great potential in cancer treatment.
研究领域:
纳米技术
·
药学
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 8
·1667
·
IF 4.6
Zenan Chen,Wei Li,Yan Zhao,Dingrui Liu,Jiahong Han,Enbo Cai
Tumorigenesis and progression are closely associated with apoptosis and primarily regulated by mitochondria, which are considered major targets for cancer therapy. In this study, twelve novel icaritin (ICT) derivatives were designed and synthesized, four of which were specifically targeted to mitochondria. Biological studies demonstrated that all compounds containing triphenylphosphine (TPP+) exhibited a substantial increase in antitumor activity compared to ICT and control compounds while also exhibiting notable selectivity for tumor cells over normal cells. Among these derivatives, Mito-ICT-4 exhibited the strongest antiproliferative effect, with an IC50value of 0.73 ± 0.06 μM for BEL-7402 cells, which is 29 times lower than that of ICT, and an IC50value of 67.11 ± 2.09 μM for HEK293 cells, indicating approximately 33-fold selectivity for tumor cells. High-performance liquid chromatography (HPLC) analysis revealed that Mito-ICT-4 significantly accumulated in the mitochondria of BEL-7402 cells, with the level of accumulation approximately 2.5 times greater than that of ICT. Further investigations demonstrated that upon entering the mitochondria of tumor cells, Mito-ICT-4 downregulated SIRT3 protein expression, disrupted intracellular redox homeostasis, and led to a substantial increase in mitochondrial ROS levels, abnormal CypD-dependent MPTP opening, mitochondrial membrane potential depolarization, and ROS release into the cytoplasm, ultimately triggering ROS-mediated apoptosis in BEL-7402 cells. Transcriptomic analysis identified differentially expressed genes and enriched pathways, highlighting the ROS-mediated p38-MAPK signaling pathway as a key mediator of Mito-ICT-4-induced mitochondria-dependent apoptosis. The effects of Mito-ICT-4 on the expression of key genes (SIRT3, CypD, P-MKK6, P-P38, and DDIT3) were further validated by qRT-PCR and Western blot analysis, with results aligning with transcriptomic data. The novel ICT derivatives synthesized in this study, with mitochondria-targeting functionality, provide a basis for the development of targeted antitumor drugs.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Zixia Wu,Weibo Xia,Liling Ou,Ling Zheng,Bingying Hou,Tonghe Pan,Wenjie Sun,Leo H Koole,Yongqing Shao,Lei Qi
Purpose Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation of ROS on the ocular surface. Here, we investigated the nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment for DED.Methods NGQDs were prepared by using citric acid and urea as precursors through hydrothermal method. The antioxidant abilities of NGQDs were evaluated through: scavenging the ROS both extracellular and intracellular, regulating the nuclear factor-erythroid 2-related factor (Nrf2) antioxidant pathway of human corneal epithelial cells (HCECs) and their transcription of inflammation related genes. Furthermore, NGQDs were modified by Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo, both the NGQDs and RGDS@NGQDs were suspended in 0.1% Pluronic F127 (w/v) and delivered as eye drops in the scopolamine hydrobromide-induced DED mouse model. Preclinical efficacy was compared to the healthy and DPBS treated DED mice.Results These NGQDs demonstrated pronounced antioxidant properties, efficiently neutralizing free radicals and activating the intracellular Nrf2 pathway. In vitro studies revealed that treatment of H2O2-exposed HCECs with NGQDs induced a preservation in cell viability. Additionally, there was a reduction in the transcription of inflammation-associated genes. To prolong the corneal residence time of NGQDs, they were further modified with RGDS peptides and suspended in 0.1% Pluronic F127 (w/v) to create RGDS@NGQDs F127 eye drops. RGDS@NGQDs exhibited superior intracellular antioxidant activity even at low concentrations (10 μg/mL). Subsequent in vivo studies revealed that RGDS@NGQDs F127 eye drops notably mitigated the symptoms of DED mouse model, primarily by reducing ocular ROS levels.Conclusion Our findings underscore the enhanced antioxidant benefits achieved by modifying GQDs through nitrogen doping and RGDS peptide tethering. Importantly, in a mouse model, our novel eye drops formulation effectively ameliorated DED symptoms, thereby representing a novel therapeutic pathway for DED management.
研究领域:
眼科
·
材料科学
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药学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2023
·
IF 3.8
Hao Zhao,Xin Lin,Qingfeng Chen,Xiaoyue Wang,Yongya Wu,Xiaoxia Zhao
Sepsis-induced cardiomyopathy (SIC) has high morbidity and mortality. Quercetin (QUE) has been used to treat many inflammatory diseases related to pyroptosis . However, its effect on SIC has not been reported before. We aimed to explore the therapeutic mechanism of QUE on SIC. We found that the expression levels of NOX2, markers of myocardial injury and inflammatory factors related to pyroptosis were upregulated in the serum of SIC patients. QUE improved the viability and reduced the death rate of LPS-treated H9C2 cells. It could downregulate the expression level of NOX2 and alleviate NOX2-induced mitochondrial damage to inhibit the ROS-mediated NF-κB/TXNIP pathway thus ameliorating cell pyroptosis. Overexpression of NOX2 partially attenuated the anti-pyroptotic effects of QUE on LPS-treated H9C2 cells in vitro. Besides, the results of animal experiments reported that the mitochondrial damage was reduced by QUE treatment, which subsequently inhibited the ROS-mediated NF-κB/TXNIP pathway to ameliorate cell pyroptosis to further alleviate myocardial injury in CLP-induced rats in vivo. To conclude, QUE suppressed the NOX2/ROS-mediated NF-κB/TXNIP signaling pathway to ameliorate pyroptosis of cardiomyocytes to relieve SIC.
研究领域:
药理学
·
心脏病学
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免疫学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Meng Sun,Nan Hu,Yangyang Gao,Nan Lv,Xiaohong Fu,Yafeng Li,Shaodong Zhai,Ruiping Zhang
Ischemia-induced myocardial injury has become a serious threat to human health, and its treatment remains a challenge. The occurrence of ischemic events leads to a burst release of reactive oxygen species (ROS), which triggers extensive oxidative damage and leads to dysfunctional autophagy, making it difficult for cells to maintain homeostasis. Antioxidants and modulation of autophagy have thus become promising strategies for the treatment of ischemic myocardial injury. This study proposes an antioxidant-activated autophagy therapeutic regimen based on combining melanin (Mel), an excellent antioxidant with metformin mimetic ploymetformin via electrostatic interactions, to obtain a nanocomplex (Met-Mel). The nanocomplex is finally encapsulated with platelet membranes (PMN) to construct a biomimetic nanoparticle (PMN@Met-Mel) capable of targeting injured myocardium. The prepared PMN@Met-Mel has good Mel loading capacity and optimal biosafety. It exhibits excellent antioxidant activity and autophagy activation, rapidly restoring mitochondrial function. Moreover, RNA sequencing (RNA-seq) analysis reveals that PMN@Met-Mel operates mechanistically by triggering the activation of the autophagy pathway. Subsequent in vivo experiments showcase promising cardioprotective effects of these nanoparticles. These discoveries present a newly devised nanoplatform with promising potential for the effective treatment of myocardial infarction.
研究领域:
心血管疾病
·
纳米医学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Fanjia Dai,Fengjiao Chen,Jiaying Zhang,Xianwu Chen,Hongze Liang,Zhenjiang Liang,Shun Zhang,Hui Tan,Lingling Zhao
The tumor microenvironment is distinguished from normal tissues, such as the acidic microenvironment, elevated reactive oxygen species (ROS) levels, and overexpressed specific receptors on the cell surface. According to these unique hallmarks of cancer, stimulus-responsive drug carriers can be designed for targeted anticancer drug delivery and specific drug release in tumor tissues. Herein, a folate-modified pH/ROS dual-responsive polymeric micellar nanosystem was developed for the targeted delivery of doxorubicin (DOX). The drug release profile suggested a sustained drug release from the polymeric micelles and an accelerated drug release at lower pH and higher ROS levels. The cellular uptake assay indicated that the polymeric micelles were internalized by HepG2 cells and that the cellular uptake of micelles can be enhanced by folate modification through a receptor-mediated endocytosis pathway. Furthermore, the folate-modified pH/ROS dual-responsive polymeric micellar nanocarriers demonstrated enhanced inhibition on the migration of HepG2 cells in the cell scratch test and showed improved suppression on the proliferation of HepG2 cells and a lower IC50 than the nonfolate micelles in the cell viability test, indicating the desirable in vitro anticancer efficiency of the nanosystem.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Luokai Wang,Yuexue Mai,Junzheng Zhang,Chujin Ruan,Jiayan Hu,Kai Ye,Yan He,Dongsheng Wang,Lulu Jin,Zhengwei Mao,Chenggang Yi,Pingfeng Yu
The emergence of multidrug-resistant pathogens has created a global public health challenge, demanding the development of efficient and safe therapeutic strategies. Herein, we present a novel nanozyme-armed phage system (PA3@RuO 2 ) designed to combat chronic Pseudomonas aeruginosa infections. This system combines the precision of phage therapy with an anti-inflammatory approach. The phage component, PA3, maintains its ability to specifically target and efficiently lyse a broad spectrum of P. aeruginosa strains. Meanwhile, RuO 2 nanozymes with reactive oxygen species-scavenging capabilities localize to infection sites, mitigating inflammation and hypoxia. This dual action enables bacterial clearance and inflammation reduction while ensuring the biocompatibility of PA3@RuO 2 with healthy tissues. In vivo studies further confirm the effectiveness of PA3@RuO 2 in treating chronic P. aeruginosa -induced wound infections and promoting tissue repair. Overall, these findings suggest that PA3@RuO 2 holds promise for developing non-antibiotic antibacterial therapies and advanced disinfection approaches.
研究领域:
微生物学
·
噬菌体疗法
·
纳米技术
·
传染病学
·
抗炎研究
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Xuan Li,Kun Xu,Ye He,Bailong Tao,Ke Li,Chuanchuan Lin,Jingwei Hu,Jing Wu,Yi Wu,Shaopeng Liu,Peng Liu,Huaiyu Wang,Kaiyong Cai
Ideal titanium implants are required to participate in bone repair actively to improve in situ osteointegration. However, the traditional surface functionalization methods of titanium implants are difficult to both achieve the active regulation and long-term stability of bioactive components. Here, a novel functionalized titanium which loaded with thymosin β4 (Tβ4) and covered by a hydrogel coating was designed and evaluated. A strong adhesion between the coating and the titanium substrate was realized by the synergistic action of borate ester bonds and surface topological structure. The hydrogel coating also achieved an in vivo adhesion between implant and tissue through hydrogen bonds and borate bonds. In addition, based on the ROS response property of borate bonds, the implant can release Tβ4 in response to the immune reaction of bone healing by regulating the polarization of macrophages, thereby reducing the fibrosis formation around the implant interface and promoting vascularization and osteointegration of bone defects.
研究领域:
生物材料
·
组织工程
·
免疫学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Xinyue Sun,Wenyue Zhang,Yuqi Wang,Yilei Zhang,Xiaojing Liu,Xu Shi,Shiwen Xu
Di(2-ethylhexyl) phthalate (DEHP) and polystyrene microplastics (PS-MPs) are new environmental pollutants that attracted increased attention. At present, the effects and underlying mechanisms of action of combined exposure of DEHP and PS-MPs on the kidney have not been elucidated. To investigate the renal toxicity of DEHP and PS-MPs exposure, we established single and combined DEHP and PS-MPs exposure models in mice and HEK293 cells, respectively. Hematoxylin and eosin staining, transmission electron microscopy , monodansylcadaverine staining, immunofluorescence, real-time quantitative PCR, Western blot analysis and other methods were used to detect relevant indicators. The results showed that the expression levels of ROS/AMPK/ULK1 and Ppargc1α/Mfn2 signaling pathway-related genes were significantly increased in the DEHP and PS-MPs exposure models. The mRNA and protein expression levels of autophagy markers were also upregulated. In addition, we found that the expression levels of mRNAs and proteins in the combined exposure group were more significantly increased than those in the single exposure group. In conclusion, combined exposure to DEHP and PS-MPs caused oxidative stress and activated the AMPK/ULK1 pathway, thereby inducing renal autophagy. Our results enhance the field of nephrotoxicity studies of plasticizers and microplastics and provide new light on combined toxicity studies of DEHP and PS-MPs.
研究领域:
毒理学
·
环境科学
·
分子生物学
·
肾脏生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zhipeng Sun,Yilin Ding,Zetao Wang,Huitong Luo,Qi Feng,Xiaodong Cao
Bacterial infection and the resulting inflammatory cascade are key factors hindering diabetic ulcers healing. The essential prerequisites for promoting diabetic ulcer healing are to sequentially achieve rapid sterilization, prevent reinfection, and modulate the inflammatory response. Inspired by the size-dependent sequential toxin release behavior of “Malaysian exploding ant”, we develop a ROS-responsive “exploding hydrogel” (E-gel) with size-dependent sequential release effects, which sequentially performs photothermal sterilization, persistent antibacterial activity, and immune regulation. Specially, polyhexamethylene guanidine (PHMG, P) and mesoporous polydopamine nanoparticles loaded with α-lipoic acid (α-LA@MPDA NPs, LD) were encapsulated into sulfhydryl-modified hyaluronic acid (HA-SH) through disulfide bonds to form a PLD/E-gel. The high temperatures generated by the photothermal effects of MPDA can kill over 90 % of bacteria within 10 min. During the swelling period of PLD/E-gel, PHMG diffuses out and effectively prevents the wound from re-infection. Along with the degradation of PLD/E-gel, submicron-sized α-LA@MPDA NPs are released from the cross-linked network to scavenge excessive ROS and modulate the inflammatory cascade. Animal experiments shows that PLD/E-gel accelerates the healing of infected diabetic wounds in SD rats by rapidly killing bacteria, inhibiting bacterial recolonization, relieving wound inflammation, and facilitating collagen deposition. To sum up, PLD/E-gel has a great application potential for diabetic wound healing.
研究领域:
材料科学
·
生物医学工程
·
药学
·
伤口愈合
·
纳米技术
·
糖尿病研究
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Panxianzhi Ni,Dengbinpei Duan,Shuting Xiong,Meng Zhong,Can Huang,Jing Shan,Tun Yuan,Jie Liang,Yujiang Fan,Xingdong Zhang
Gastric ulcer (GU) is currently one of the most serious and common gastrointestinal diseases worldwide, severely affects the quality of life of patients. However, treatment strategies have limitations, such as drug safety and lack of repair specificity. In this work, we developed a polyethyleneimine/polyacrylic acid/lactose-modified chitosan (PPCL) hydrogel to repair gastric ulcers. This hydrogel was characterized by robust tissue adhesion, low swelling rate, gastric acid fluid resistance, potent antioxidants and good biocompatibility, which could act as a physical barrier to prevent gastric acid and digestive enzymes from further destroying ulcers. In vivo data from a rat GU model confirmed that this hydrogel effectively promoted gastric ulcer healing, and the therapeutic effect was better than that of commercial gastric mucosal protectants. Further mechanistic research identified that the hydrogel accelerated GU healing by alleviating oxidative stress, promoting reepithelization, angiogenesis and mucosal repair. Our findings revealed that the PPCL hydrogel provides a promising therapeutic approach for healing gastric ulcer.
研究领域:
药理学
·
材料科学
·
生物医学工程
·
胃肠病学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）