DYES AND PIGMENTS
·
2024
·
IF 4.1
Zhijia Sheng,Chao Zhao,Xiaoyan Huang,Jing Wang,Yi Liu
Hypoxia is a common feature of solid tumors and is considered to be the fatal flaw of conventional photodynamic therapy (PDT), which severely reduces the overall therapeutic efficacy. Here, we developed a series of halogenated photosensitizers to address this issue. The results showed that the introduction of heavy atoms enhanced the spin-coupling effect of the photosensitizers and effectively improved the type I PDT (non-oxygen-dependent) efficiency. The preferred iodine-substituted photosensitizer NRh–I was used as the basic architecture, and further nitrosyl modification was performed to obtain the NO small-molecule prodrug, which was finally encapsulated with DSPE-mPEG 5k to obtain a biocompatible NO nanophotocontrolled prodrug. By using the enhanced permeability and retention effect (EPR), the prodrug system can precisely target the lesion site, release a high concentration of NO by photocontrol, kill the tumor cells, and at the same time, cascade with ROS released with the same “time-space” precision to generate higher cytotoxicity, ONOO − , which generates a stronger targeted synergistic therapeutic effect. This “butterfly effect” strategy maximizes the effect of PDT and broadens the idea of translational medicine.
研究领域:
癌症治疗
·
药学
·
生物医学工程
·
化疗
✓ 已验证
DOI
高影响因子
Small
·
2021
·Vol. 18
·期 9
·2104120
·
IF 13.281
Ziyu Wu,Rui Wu,Xiaoyun Li,Xingwen Wang,Xueting Tang,Kaiyuan Tan,Mimi Wan,Chun Mao,Xingquan Xu,Huiming Jiang,Jiawei Li,Min Zhou,Dongquan Shi
Most of the current non-pharmacological treatment strategies for atherosclerosis (AS) suffer from poor penetration into the plaque and only aim at a certain factor in its formation process, resulting in limited therapeutic effect. Herein, a kind of nanomotor with dual-mode propulsion is constructed, which is sensitive to higher reactive oxygen species (ROS) at the AS site and near-infrared (NIR) laser by the covalent binding and self-assembly of β-cyclodextrin (β-CD) and L-arginine (LA) with immobilization of Au nanoparticles. NIR laser irradiation can be used as a driving force and to ablate inflammatory macrophages through the photothermal effect. The nitric oxide (NO) released by the nanomotors can be used as another driving force and a therapeutic agent to promote endothelial repair in the plaque site. LA can eliminate ROS in the inflammatory site, and β-CD can promote the removal of cholesterol from foam cells. In particular, the two driving modes of nanomotors synergistically promote their aggregation and penetration in the plaque. This kind of nanomotor can regulate the microenvironment of AS in multiple ways, including combination therapy for endothelial repair, lipid clearance, and reducing ROS, which is expected to become a potential non-pharmacological strategy in the treatment of AS.
研究领域:
纳米技术
·
生物医学工程
·
治疗学
·
心血管疾病
✓ 已验证
DOI
PubMed
高影响因子
FITOTERAPIA
·
2018
·
IF 2.642
Hong-Bo Xu,Tong-Hua Yang,Pei Xie,Zhi-Shu Tang,Xiao Song,Huai-Li Xu,Yan-Hong Li,Dong-Bo Zhang,Yan-Ru Liu,Yan-Ni Liang,Yu Zhang,Shi-Jun Liu,Si-Min Wei,Chen Sun,Hong-Bo Liu,Chong Deng,Wei Wang
Gracilistones A ( 1 ) and B ( 2 ), two new eudesmane-type sesquiterpenoids with an unusual tetrahydrofuran-fused 6/6/5 tricyclic ring system, were obtained from Acanthopanax gracilistylus under the guidance of LC-MS investigation. Their structures and absolute configurations were assigned by extensive spectroscopic analyses and quantum calculation methods. Compounds 1 and 2 showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, compared with the positive control L-NMMA. In addition, compounds 1 and 2 were also evaluated for their antioxidant (DPPH • and ABTS •+ ) and xanthine oxidase (XO) inhibitory activities, and they exhibited weak inhibitory effects at 100 μM.
研究领域:
药用植物学
·
药物化学
·
炎症研究
·
天然产物化学
✓ 已验证
DOI
PubMed
高影响因子
ChemMedChem
·
2023
·Vol. 18
·期 23
·e202300468
·
IF 3.4
Jingjie Fang,Ziyi Shang,Kumaravel Kaliaperumal,Zhiran Ju,Fen-Er Chen
Graphical This study presents a design strategy, synthesis, and evaluation of balanced COX inhibitors derived from natural anti-inflammatory ascidian metabolites and celecoxib, highlighting their potential therapeutic value in the context of inflammation. The serious adverse effects caused by non-selective and selective cyclooxygenase-2 (COX-2) inhibitors remain significant concerns for current anti-inflammatory drugs. In this study, we present the design and synthesis of a novel series of celecoxib analogs incorporating a hydrazone linker, which were subjected to in silico analysis to compare their binding poses with those of clinically used nonsteroidal anti-inflammatory drugs (NSAIDs) against COX-1 and COX-2. The synthesized analogs were evaluated for their inhibitory activity against both COX enzymes, and compound 6 m , exhibiting potent balanced inhibition, was selected for subsequent in vitro anti-inflammatory assays. Treatment with 6 m effectively suppressed the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages, resulting in reduced expression of pro-inflammatory factors such as inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), IL-1β, as well as decreased production of prostaglandin E 2 (PGE 2 ), nitric oxide (NO), and reactive oxygen species (ROS). However, 6 m has no effect on the MAPK signaling pathway. Therefore, due to its potent in vitro anti-inflammatory activity coupled with lack of cytotoxicity, 6 m represents a promising candidate for further development as a new lead compound targeting inflammation.
研究领域:
药理学
·
药物化学
·
炎症研究
·
药物设计
✓ 已验证
DOI
PubMed
高影响因子
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