JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Pang Wenyang,Cao Yin,Du Shuang,Liang Zuowen,Wang Hongliang,Liu Lingyun
Background Tire wear particles (TWPs) are a major source of micro- and nanoplastics. However, reports on nanoscale tire wear particles, especially regarding their potential hazards to the male reproductive system, remain scarce. Results Here, we examined whether nanoscale tire wear particles impair spermatogenesis and blood-testis barrier integrity through ROS-linked ferroptotic injury. Using a 70-day oral exposure model in pubertal male mice and complementary GC-2 and TM4 cell models, we found that high-dose particle exposure reduced epididymal sperm density, increased sperm abnormalities, disrupted seminiferous epithelial organization, and increased BTB permeability. TWPs shifted metabolomic profiles toward lipid and iron dysregulation, suppressed SLC7A11/GPX4, increased ACSL4 and labile Fe²⁺, and depleted junctional proteins. Ferrostatin-1 reduced lipid peroxidation, iron accumulation, cell death, and junctional protein loss, indicating a functional contribution of ferroptosis. Mechanistically, TWPs first induced total and mitochondrial reactive oxygen species and mitochondrial depolarization, which were restrained by N-acetylcysteine. Downstream, autophagic ferritin degradation amplified ferroptotic injury, as chloroquine or NCOA4 knockdown preserved ferritin, reduced malondialdehyde accumulation, restored GPX4/SLC7A11, and improved viability. NCOA4 depletion did not substantially blunt ROS induction, placing ferritinophagy after redox imbalance. Conclusions Together, these data define a ROS-initiated, NCOA4-dependent ferritinophagy-ferroptosis axis that connects nanoscale TWPs to BTB failure and impaired spermatogenic homeostasis. This work provides a mechanistic basis for future assessment of reproductive health risks associated with TWPs exposure. Graphical abstract
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2020
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IF 5.573
Jianqiang Qian,Zhongyuan Xu,Chi Meng,Ji Liu,Pei-Ling Hsu,Yangyang Li,Weizhong Zhu,Yumin Yang,Susan L. Morris-Natschke,Kuo-Hsiung Lee,Yanan Zhang,Yong Ling
Oxidative therapy, a strategy that specifically increases reactive oxygen species (ROS) levels in tumor cells by disrupting the redox homeostasis has gained increasing interest. The antitumor effects of the natural product piperlongumine (PL) appear to result from its ability to increase intracellular ROS levels via inhibition of antioxidative thioredoxin reductase (TrxR). Twenty-seven benzylidenecyclohexenone-based PL analogues ( 2a-v and 15a-e ) were designed, synthesized and evaluated for their pharmacological properties . Most of the compounds exhibited potent antiproliferative activities against five human cancer cell lines, especially against breast tumor cells. One of the most promising analogueues 2c showed 12-fold higher inhibitory activity against the thioredoxin reductase (TrxR) than PL and surpressed the expression of TrxR1 protein in breast cancer cells and inhibited TrxR enzymatic activity . In addition, 2c increased ROS levels and resulted in marked apoptosis by regulating apoptosis-related proteins expressed in the breast cancer cells. Compound 2c also triggered the formation of autophagosomes and autolysosomes by promoting the expression of LC3-II and Beclin-1 and diminishing the expression of LC3-I and p62 proteins. Finally, 2c displayed low acute toxicity and good inhibitory potency to tumors in mice. Overall, 2c is a promising anti-breast cancer candidate warranting further investigation.
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CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Weiyong Tao,Xiaodan Wu,Jiaqi Li,Feige Wu,Chen Chen,Ting Jiang,Cunjing Xu,Shangtong Jiang,Jianglin Wang,Bo Xiao,Yingying Du,Shengmin Zhang
The anti-cancer effect of selenite (SeO 3 2− ) is limited by its short half-life and narrow therapeutic window. Peroxynitrite (ONOO − ), the most active reactive nitrogen species (RNS) derived from nitric oxide (NO) reacting with superoxide anion (O 2 •− ), is still not fully exploited in the combination therapy against cancers. Herein, an injectable hydrogel is developed to trigger intracellular reactive oxygen species (ROS)/RNS bursts and disrupt nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis via an innovative SeO 3 2− -based strategy. Calcium selenite/ L -Arginine ( L -Arg) nanospheres (SL NPs) are synthesized as the donor of NO and SeO 3 2− . The injectable Alg@SLGA sol composed of SL NPs, glucose oxidase (GOx), 6-aminonicotinamide (6-AN, an inhibitor of the pentose phosphate pathway (PPP)), and sodium alginate (Alg) can convert to gel in a physiological environment. Peritumoral injection of Alg@SLGA hydrogel is performed for safe and targeted treatment. The loaded GOx catalyzes glucose oxidation to produce acidic H 2 O 2 , initiating the release of NO and SeO 3 2− from Alg@SLGA. SeO 3 2− reacts with intracellular GSH and H 2 O 2 to generate •OH and O 2 •− , which further interacts with NO to form ONOO − . The SeO 3 2− and 6-AN synergistically trigger intracellular NADPH exhaustion by promoting cystine metabolism-mediated NADPH consumption and inhibiting NADPH generation, respectively. Moreover, Alg@SLGA effectively induces immunogenic cell death (ICD) of tumor cells, further provoking systemic antitumor immune responses. As a consequence, the injectable Alg@SLGA hydrogel achieves enhanced ROS/RNS-mediated combination therapy by synergistically disrupting NADPH homeostasis and improving antitumor immunity.
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Advanced Healthcare Materials
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2023
·
IF 10
Yupeng Guan,Hanqi Lei,Chengyuan Xing,Binyuan Yan,Bingbiao Lin,Xiangwei Yang,Hai Huang,Yang Kang,Jun Pang
Chemotherapy remains the most essential treatment for prostate cancer, but multidrug resistance (MDR) contributes to chemotherapy failure and tumor-related deaths. The overexpression of P-glycoprotein (P-gp) is one of the main mechanisms behind MDR. Here, we report a multimodal nanoplatform with a reactive oxygen species (ROS) cascade for gas therapy/ferroptosis/chemotherapy in reversing MDR. The nanoplatform disassembles when responding to intracellular ROS and exerts three main functions: First, NO-targeted delivery could reverse MDR by downregulating P-gp expression and inhibiting mitochondrial function. Second, ferrocene-induced ferroptosis breaks the redox balance in the tumor intracellular microenvironment and synergistically acts against the tumor. Third, the release of paclitaxel is precisely controlled in situ in the tumor for chemotherapy that avoids damage to normal tissues. Excitingly, this multimodal nanoplatform is a promising weapon for reversing MDR and may provide a pioneering paradigm for synergetic cancer therapy. This article is protected by copyright. All rights reserved
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KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
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2023
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IF 3.3
Peng-Cheng Zhong,Zhi-Wen Liu,Qi-Chang Xing,Jia Chen,Rui-Pei Yang
Non-small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF-β and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial–mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus-mediated gain-of-function studies of TGF-β and MST1 were applied to validate the roles of TGF-β and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF-β expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF-β in either in vitro or mouse-transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF-β to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Xiaofei Wang,Hongxiu Wei,Yangcen Ou,Zhen Li,Feng Luo,Hong Tan,Jiehua Li
Development of an inflammation modulating polypropylene (PP) mesh in pelvic floor repair is an urgent clinical need. This is because PP mesh for pelvic floor repair can cause a series of complications related to foreign body reactions (FBR) in postoperative period. Therefore, we successfully prepared PP composite mesh that can scavenge reactive oxygen species (ROS) and inhibit inflammation to moderate FBR by a simple method. First, a pregel layer was formed on PP mesh by dip coating. Among them, polyurethane with polythioketal (PTK) is an excellent ROS scavenger, and dopamine methacrylamide (DMA) improves the stability of the coating and synergistically scavenges ROS. Then, a composite mesh (optimal PU50-PP) was obtained by photopolymerization. The results showed that the polyurethane gel layer was able to scavenge more than 90% of free radicals and about 75% of intracellular ROS. In vitro , PU50-PP mesh significantly scavenged ROS and resisted macrophage adhesion. After implantation in the posterior vaginal wall of rats, PU50-PP eliminated 53% of ROS, inhibited inflammation (decreased IL-6, increased IL-10), and dramatically reduced collagen deposition by about 64%, compared to PP mesh. Thus, the composite PP mesh with ROS scavenging and anti-inflammatory properties provides a promising approach for mitigating FBR.
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Advanced Science
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2023
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IF 15.1
Jiayin Yu,Zhihao Guo,Jiachang Yan,Changxin Bu,Chang Peng,Cuie Li,Rui Mao,Jian Zhang,Zhi Wang,Shi Chen,Meicun Yao,Zhiyong Xie,Chuan Yang,Yi Yan Yang,Peiyan Yuan,Xin Ding
Helicobacter pylori ( H. pylori ) has infected more than half of the world's population, and is the major cause of gastric cancer. The efficacy of standard antibiotic-based triple therapy is declining due to drug resistance development. Herein, a pH-responsive reactive oxygen species (ROS) nanogenerator (Fe-HMME@DHA@MPN) composed of acid-responsive metal polyphenol network (MPN) shell and mesoporous metal-organic nanostructure core [Fe-HMME (hematoporphyrin monomethyl ether, sonosensitizer)] loaded with dihydroartemisinin (DHA) is reported. These nanoparticles generate more ROS singlet oxygen than sonosensitizer HMME under ultrasonication, and this sonodynamic process is fueled by oxygen generated through Fenton/Fenton-like reactions of the degraded product in gastric acid Fe (II) and hydrogen peroxide (H 2 O 2 ) in the infection microenvironment. The encapsulated DHA, as a hydroperoxide source, is found to enhance the peroxidase-like activity of the Fe-HMME@DHA@MPN to generate ROS hydroxyl radical, beneficial for the microenvironment without sufficient H 2 O 2 . In vitro experiments demonstrate that the ROS nanogenerators are capable of killing multidrug-resistant H. pylori and removing biofilm, and ROS nanogenerators show high therapeutic efficacy in a H. pylori infection mouse model. Unlike the triple therapy, the nanogenerators display negligible side effects toward the normal gut microbiota. Taken together, these self-enhanced ROS nanogenerators have a great potential for treatment of H. pylori infection.
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CARBOHYDRATE POLYMERS
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2023
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IF 11.2
Xiaomei Dai,Xiaojun Liu,Yu Li,Qingqing Xu,Lele Yang,Feng Gao
Staphylococcus aureus ( S. aureus ) residing in host macrophages is hard to clear because intracellular S. aureus has evolved mechanisms to hijack and subvert the immune response to favor intracellular infection. To overcome this challenge, nitrogen-phosphorous co-doped carbonized chitosan nanoparticles (NPCNs), which possess the polymer/carbon hybrid structures, were fabricated to clear intracellular S. aureus infection through chemotherapy and immunotherapy. Multi-heteroatom NPCNs were fabricated through the hydrothermal method , where chitosan and imidazole were used as the C and N sources and phosphoric acid as the P source. NPCNs can not only be used as a fluorescent probe for bacteria imaging but also kill extracellular and intracellular bacteria with low cytotoxicity. NPCNs could generate ROS and polarize macrophages into classically activated (M1) phenotypes to increase antibacterial immunity. Furthermore, NPCNs could accelerate intracellular S. aureus -infected wound healing in vivo. We envision that these carbonized chitosan nanoparticles may provide a new platform for clearing intracellular bacterial infection through chemotherapy and ROS-mediated immunotherapy.
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BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Baiyi Yan,Yanchun Gong,Wei Meng,Huizhen Sun,Wenxi Li,Kaizhi Ding,Caixia Dang,Xiaofei Gao,Wei Sun,Chunhua Yuan,Songhua Wang,Li-Hua Yao
Type 2 diabetes mellitus (T2DM) is a common and multiple endocrine metabolic disease. When pancreatic β cell in case of dysfunction, the synthesis and secretion of insulin are reduced. This study is to explore the effect of cordycepin (the molecular formula C 10 H 13 N 5 O 3 ), a natural adenosine isolated from Cordyceps militaris , on high glucose/lipid-induced glucotoxicity and lipotoxicity in INS-1 cells. Our results showed that cordycepin improved cell viability, improved cell energy metabolism and promoted insulin synthesis and secretion. The mechanism may be related to that cordycepin reduces intracellular reactive oxygen species (ROS), increases ATP content in cells, causes membrane depolarization and balances the steady state of Ca 2+ concentration, cordycepin inhibits cell apoptosis, which may be related to the downregulation of proteins level of c-Jun N-terminal kinases (JNK) phosphorylation, cytochrome c (Cyt-c), Cleaved Capase-3, the mRNA level of JNK, Cyt-c, Capase-3 and upregulation of proteins/mRNA level of pancreatic and duodenal homeobox factor-1 (PDX-1). These results suggest that cordycepin can inhibit cell apoptosis and protect cell number by downregulating ROS/JNK mitochondrial apoptosis pathway under high glucose/lipid environment, thereby improving the function of pancreatic islet cells, providing a theoretical basis for the related research on the prevention and control of cordycepin on T2DM.
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Journal of Materials Chemistry B
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2019
·Vol. 7
·期 42
·6630-6642
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IF 5.047
Nil Kanatha Pandey,Lalit Chudal,Jonathan Phan,Liangwu Lin,Omar Johnson,Meiying Xing,J. Ping Liu,Haibin Li,Xuejing Huang,Yang Shu,Wei Chen
Copper–cysteamine (Cu–Cy) is a novel sensitizer that can be excited by ultraviolet (UV) light, microwave (MW), ultrasound, and X-rays to generate highly toxic reactive oxygen species (ROS) for cancer cell destruction. The purpose of this study is to present a facile method for the synthesis of Cu–Cy nanoparticles. Interestingly, we were able to decrease both the stirring and heating time by about 24 and 6 times, respectively, thus making Cu–Cy nanoparticles more economical than what was reported before. 1,4-Diazabicylo[2.2.2]octane (DABCO), a well-known singlet oxygen quencher, showed that the majority of ROS produced by Cu–Cy nanoparticles upon UV and MW exposure were singlet oxygen. Moreover, ROS generated by Cu–Cy nanoparticles upon UV and MW exposure were confirmed by a known ROS tracking agent, dihydrorhodamine 123, further serving as an additional piece of evidence that Cu–Cy is a promising ROS generating agent to destroy cancer cells as well as bacteria or viruses by a radical therapeutic approach. Additionally, for the first time, the hydroxyl radical (˙OH) produced by Cu–Cy nanoparticles upon MW activation was proved by a photoluminescence (PL) technique using coumarin as a probe molecule. Remarkably, newly synthesized nanoparticles were found to be much more effective for producing ROS and killing cancer cells, suggesting that the new method may have increased the reactivity of the Cu–Cy nanoparticles due to an overall size reduction. Overall, the new method not only reduced the synthesis time but also enhanced the effectiveness of Cu–Cy nanoparticles for photodynamic therapy.
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Biomaterials Science
·
2019
·Vol. 7
·期 9
·3683-3692
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IF 5.251
Zongjun Liu,Tuo Li,Fang Han,You Wang,Yang Gan,Junhui Shi,Tianran Wang,Muhammad Luqman Akhtar,Yu Li
Synergistic cancer starvation/ROS-mediated/chemo-therapy is developed through a cascade reaction with enzyme glucose oxidase (GOX) modified on the surface of an Fe-based metal organic framework (MOF(Fe)) and drug camptothecin (CPT) loaded into the cavities of MOF(Fe). Once internalized by tumor cells, GOX catalyzes endogenous glucose into hydrogen peroxide (H2O2) and gluconic acid (H+) enabling starvation therapy through choking off energy (glucose) supply. Meanwhile, the acidic micro-environment of tumor enhanced by the generated H+ degrades the MOF(Fe) simultaneously releasing CPT for chemotherapy and Fe3+, catalyzing H2O2 into one of the strongest reactive oxygen species (ROS) ˙OH enabling ROS-mediated therapy. Both in vitro and in vivo results show remarkable tri-modal synergistic anticancer effects. This work may shed some light on the development of novel multi-modal cancer therapies without any external intervention.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Zhen He,Xiangyun Tan,Ming Yuan,Liang Chen,Yan Meng,Qi Wang,Junjie Hu,Zhenpeng Qiu,Yuan Yang
Acute liver injury (ALI) is a prevalent form of hepatic disease associated with significant morbidity and mortality due to medical treatments, exposure to toxins or viral infections. Anethole trithione (ATT) is a heterocyclic sulfur compound recognized for its chemoprotective properties against cancer and drug-induced toxicity. This study aimed to evaluate the effectiveness of ATT in the treatment of ALI. The therapeutic effects of ATT on hepatic injury were evaluated in vivo by inducing ALI in mice through the administration of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). Additionally, HepG2 and Huh7 cells exposed to LPS were utilized to investigate the underlying mechanisms in vitro. The results indicated that ATT significantly reduced the production of reactive oxygen species (ROS), mitigated oxidative stress-related biochemical markers, and inhibited hepatocyte apoptosis in vivo, resulting in marked improvement in ALI in the murine model. Mechanistic studies conducted both in vivo and in vitro demonstrated that ATT alleviates LPS/D-Gal-induced ALI by inhibiting ROS production and the activity of nuclear factor-kappa B (NF-κB). Collectively, these findings underscore the potential therapeutic benefits of ATT in the management of ALI.
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