MOLECULAR PHARMACEUTICS
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2022
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IF 5.364
Ying Chen,Xiaoming Liao,Pei Jing,Liangkui Hu,Zengqiu Yang,Yongchao Yao,Chunyan Liao,Shiyong Zhang
As the most common subtype in ovarian malignancies, high-grade serous ovarian cancer (HGSOC) made less therapeutic progress in past decades due to the lack of effective drug-able targets. Herein, an effective linoleic acid (LA) and glucosamine (GlcN) hybrid (LA–GlcN) was synthesized for the treatment of HGSOC. The GlcN was introduced to recognize the glucose transporter 1 (GLUT 1) overexpressed in tumor cells to enhance the uptake of LA–GlcN, and the unsaturated LA was employed to trigger ferroptosis by iron-dependent lipid peroxidation. Since the iron content of HGSOC was ∼5 and 2 times, respectively, higher than that of the normal ovarian cells and low-grade serous ovarian cancer cells, these excess irons make them a good target to enhance the ferroptosis of LA–GlcN. The in vitro study demonstrated that LA–GlcN could selectively kill HGSOC cells without affecting normal cells; the in vivo study revealed that LA–GlcN at the dose of 50 mg kg–1 achieved a comparable tumor inhibition as doxorubicin hydrochloride (4 mg kg–1) while the overall survival of mice was extended largely due to the low toxicity, and when the dose was increased to 100 mg kg–1, the therapeutic outcomes could be improved further. This dietary hybrid which targets the excess endogenous iron to activate ferroptosis represents a promising drug for HGSOC treatment.
研究领域:
肿瘤学
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药物化学
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生物医学工程
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Zhipeng Zhang,Rui Liu,Wei Zheng,Yaqiong Lan,Yongmei Li,Lujun Chen
In this study, a ternary co-fermentation system was developed using iron-phosphorus precipitates (FePs)-bearing sludge, peroxydisulfate (PDS), and corn gluten meal (CGM) to activate PDS through a microbe-mediated endogenous iron cycle, thereby promoting phosphorus (P) release and acidogenesis. Fe(II) was released along with P via the dissolution of Fe(II)Ps, resulting from Fe(III)Ps bioreduction. Subsequently, the released Fe(II) induced PDS activation, which avoided the negative impact of external activators on P release by precipitation with P. The optimal PDS dosage for ternary co-fermentation was 0.2 mM/g TSS. At this dosage, P release efficiency increased from 27.3 % (sludge-only group) to 71.6 % and volatile fatty acids (VFAs) production increased from 41.0 (sludge-only group) to 158.5 mg COD/g VSS. SO 4 ·− and ·OH generated through PDS activation disintegrated sludge flocs to promote encapsulated Fe(II)Ps dissolution and organics release. The concentration of soluble chemical oxygen demand in the sludge-CGM-PDS group was 4.4 times greater than that in the sludge-only group. The increased content and biodegradability of hydrolysates (e.g., protein-like, tryptophan-like, and tyrosine-like substances) contributed to the enrichment of hydrolytic-acidogenic bacteria, resulting in a relative abundance of 40.7 %. Unclassified_c__Ignavibacteria , Clostridium , and Rubrivivax were the dominant hydrolytic-acidogenic biomarkers, which enhanced the intracellular metabolisms of glycolysis, amino acid degradation, and acetogenesis, leading to notable increases in VFAs yields. The relative abundance of phosphate acetyltransferase, a key enzyme in acetate biosynthesis, increased by 8.9 %, thus facilitating acetogenesis. In addition, unclassified_c__Ignavibacteria , as putative iron reducers, were the primary microbes mediating endogenous iron reduction. This study provides valuable insights into the PDS self-activation mechanism and microfloral traits during ternary co-fermentation, contributing to the valorization of FePs-bearing sludge waste.
研究领域:
环境工程
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微生物学
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废水处理
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
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2025
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IF 4.5
Ying Chen,Qin Ma,Jun Zhang,Jianhang Li,Yu’e Wang,Yongchao Yao,Yang Ding,Xin Dai,Xinghong Luo,Linjing Wu,Ling Tao,Xiangchun Shen
Due to the increased expression of iron storage proteins in cancer cells, utilizing the endogenous iron-catalyzed Fenton reaction for cancer ferroptosis therapy has recently emerged as a prominent research focus. However, endogenous iron primarily exists within ferroxidase FTH1 in the Fe (III)-bound state, hindering the effective catalysis of the Fenton reaction. Herein, an endogenous iron(II) self-enriched Fenton nanocatalyst (BAI@cLANCs) is fabricated by encapsulating the FTH1 inhibitor baicalin (BAI) in cross-linked lipoic acid nanocarriers (cLANCs) to amplify endogenous ferroptosis. Once internalized, BAI@cLANCs are disrupted by glutathione (GSH) in tumor cells to release BAI, which inhibits FTH1 activity and hinders Fe2+ oxidation. Meanwhile, cLANCs degrade into dihydrolipoic acid (DHLA), which reduces Fe3+ to Fe2+, synergically enriching endogenous Fe2+. Simultaneously, both BAI and DHLA stimulate H2O2 production and facilitate the Fenton reaction to produce abundant ·OH, thereby triggering lipid peroxidation and inducing tumor ferroptosis. Moreover, the reduction of Fe3+ to Fe2+ depletes GSH, facilitating ·OH production and inactivating glutathione peroxidase-4, ultimately amplifying tumor ferroptosis. Overall, this work highlights the potential of an endogenous iron(II) self-enriched Fenton nanocatalyst for cancer ferroptosis therapy, providing a paradigm for amplifying endogenous ferroptosis by inhibiting FTH1 activity and reducing iron(III) to enrich endogenous iron(II).
研究领域:
癌症治疗
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纳米技术
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生物化学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Shuang Li,Bingjie Wang,Jiaojiao Tao,Yu Dong,Teng Wang,Xia Zhao,Tianze Jiang,Lianxiao Zhang,Hai Yang
Chemodynamic therapy (CDT) is a promising strategy for cancer treatment, however, its application is restricted by low hydrogen peroxide (H 2 O 2 ) concentration, insufficient reactive oxygen species (ROS) generation, and high glutathione (GSH) levels. Here, we developed an injectable thermosensitive hydrogel (DSUC-Gel) based on “sea urchin-like” copper sulfide nanoparticles (UCuS) loaded with dihydroartemisinin (DHA) and sulfasalazine (SAS) to overcome these limitations of CDT. DSUC was cleaved to release DHA, SAS and Cu 2+ under acidic tumor microenvironment to enhance CDT. DHA with peroxide bridge responded to intracellular Fe 2+ to alleviate H 2 O 2 deficiency. SAS prevented GSH synthesis by targeting SLC7A11 and inhibited glutathione peroxidase (GPX4) activity to induce endogenous ferroptosis. ROS produced by Fenton-like reaction of Cu 2+ promoted lipid peroxidation (LPO) accumulation to promote ferroptosis. Enhanced CDT and ferroptosis induced immunogenic cell death (ICD), promoted dendritic cells (DCs) maturation and cytotoxic T lymphocytes (CTLs) infiltration. As a result, DSUC-Gel significantly inhibited tumor growth both in vitro and in vivo . Our study provides a novel approach for enhancing anti-tumor efficacy by combining CDT, endogenous ferroptosis and ICD.
研究领域:
癌症治疗
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纳米技术
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生物化学
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免疫学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）