Advanced Healthcare Materials
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2025
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IF 9.6
Lu Liu,Daiyong Chao,Qing Dong,Xianli Zhang,Kai Zhang,Zhenyu Ju
Doxorubicin (DOX), a potent anthracycline chemotherapeutic agent, is widely used in cancer treatment but is associated with significant adverse effects, particularly DOX-induced cardiomyopathy (DIC). DIC pathogenesis involves the generation of reactive oxygen species (ROS) and ferroptosis induction. Novel therapeutic strategies targeting antioxidant defenses and ferroptosis inhibition are essential for mitigating DIC. An innovative bimetallic metal-organic framework (MOF), NiCu-MOF (NCM), is developed, exhibiting multifaceted antioxidant enzyme-mimicking activities that effectively scavenge a broad spectrum of ROS. Additionally, the bimetallic NCM exhibits excellent iron-chelating ability. In vitro experiments demonstrate that NCM significantly reduces cardiomyocyte death by attenuating ROS levels and inhibiting ferroptosis. Furthermore, in a mouse model of DIC, NCM treatment results in substantial myocardial protection, evidenced by improved cardiac function and structural integrity. This protective effect is attributed to suppression of ferroptosis, preservation of mitochondrial function, and attenuation of inflammatory responses. Collectively, these findings highlight biocompatible NCM's potential as a novel cardioprotective agent and offer a promising therapeutic strategy for managing DIC.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Qianqian Zhao,Ting Wu,Chunming Tang,Jie Li,Min Wu,Jie Wu,Zhiji Wang,Yinxin Zhu,Huae Xu,Xiaolin Li
Combination chemotherapy is considered more effective than monotherapy in enhancing clinical outcomes. Ferroptosis, a unique form of regulated cell death, has been demonstrated to inhibit tumor growth and progression. Consequently, combining ferroptosis with chemotherapy represents a promising and innovative approach to antitumor therapy. In this study, we developed a novel TMTP1-modified biomimetic nanocrystal (TRNC@P + L) for the co-delivery of PTX and LF3, aiming to achieve ferroptosis-combined chemotherapy in gastric cancer. TRNC@P + L, which incorporates a tumor-homing peptide-modified red blood cell membrane, demonstrated efficient tumor targeting, prolonged circulation, enhanced drug bioavailability, and reduced non-specific toxicities of free PTX and LF3. By utilizing the synergistic effects of PTX and LF3, TRNC@P + L combination therapy significantly inhibited tumor growth, as demonstrated by both in vitro and in vivo studies. Mechanistically, TRNC@P + L triggers ferroptosis in tumor cells by downregulating GPX4 expression, the promotion of ROS accumulation, and the enhancement of lipid peroxidation. These processes synergistically enhance the anticancer efficacy of PTX.
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BIOMATERIALS
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2024
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IF 12.8
Pingting Ye,Chunhui Wang,Yixuan Wen,Kang Fang,Qi Li,Xin Zhang,Jingxian Yang,Ruihao Li,Mengyao Chen,Xiaohan Tong,Shuo Shi,Chunyan Dong
Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer due to poor immunogenicity and limited immune cell infiltration, efficient therapeutics are still deficiency. Ferroptosis, a reactive oxygen species (ROS)-reliant cell death, can enhance cellular immunogenicity and then active immune system. To sustain a long-term “hot” tumour immune microenvironment (TIME), an immune-modulator is indispensable. Metformin (MET), a commonly used oral drug for type 2 diabetes, has played a vital role in fostering an immunostimulatory environment. Herein, we confirm the TIME can be remodeled by MET and further promotes ferroptosis via upregulating cellular concentration of l -Glutamine. In light of this, we have design a self-assembled MET-loaded Fe 3+ -doped polydopamine nanoparticle (Fe-PDA-MET NP) that can disorder the cellular redox homeostasis and induce robust ferroptosis under 808 nm irradiation, resulting in a strong immune response. Based on the function of MET, there is a marked increase in the infiltration of activated CD8 + T cells and NK cells, which subsequently augments ferroptosis to a greater extent. Taken together, Fe-PDA-MET NPs activate a ferroptotic positive-feedback loop for effectively control TNBC progression, which offers a promising therapeutic modality to enhance the immunogenicity and reshape the TIME.
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Nano Today
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2024
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IF 13.2
Chenghui Liu,Mingzhu Lv,Qiqi Xu,Jiani Xie,Yong You,Kun Guo,Guohui Jiang,Lingmi Hou,Hanfeng Yang,Yuan Yong
Chronic wounds are a serious complication for diabetic patients, causing substantial inconvenience and significant economic burden to patients, due to their characteristics of sequential development encountering bacterial infections, excessive reactive oxygen species (ROS)-induced inflammation and M1 macrophage accumulation. Herein, we developed a chronological adaptive Fe-based polyoxometalate on hyaluronic acid (Fe-POM@HA) hydrogel for diabetic chronic wounds, whose capacity can be strengthened by synergistic the acid-activated and glutathione-enhanced NIR-II photothermal therapy and achieving spatiotemporal selective and adaptive inhibition of bacterial infection. During the bacteria-infection slightly acidic stage, Fe-POM catalyzes endogenous H 2 O 2 for ROS generation inducing bacterial ferroptosis, suppressing glutathione peroxidase activity, and promoting lipid peroxidation to disrupt the bacterial biofilm. As the wound transitions to neutral inflammation stage, Fe-POM with Fe 2+ /Mo 5+ mixed valences can simultaneously alleviate oxidative stress and overcome the hypoxia microenvironment by continuously scavenging excessive ROS for endogenous H 2 O 2 cyclic accumulation and O 2 sustainable replenishment. Importantly, the Fe-POM@HA hydrogel could further promote wound angiogenesis at the new tissue proliferation stage through the immunomodulation of macrophage polarization and inflammatory factor expression. Therefore, Fe-POM@HA hydrogel provides a promising chronologically adaptive protocol for the repair and regeneration of chronic cutaneous wounds addressing complex clinical demands.
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International Journal of Nanomedicine
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2024
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IF 6.6
Minghui Li,Jiabi Wu,Tao Yang,Yuhang Zhao,Ping Ren,Lingling Chang,Pilong Shi,Jing Yang,Yuhang Liu,Xiaolei Li,Peng Wang,Yonggang Cao
Background Cardiac microvascular damage is substantially related with the onset of myocardial ischaemia-reperfusion (IR) injury. Reportedly, allicin (AL) effectively protects the cardiac microvascular system from IR injury. However, the unsatisfactory therapeutic efficacy of current drugs and insufficient drug delivery to the damaged heart are major concerns. Here, inspired by the natural interaction between neutrophils and inflamed cardiac microvascular endothelial cells (CMECs), a neutrophil membrane-camouflaged nanoparticle for non-invasive active-targeting therapy for IR injury by improving drug delivery to the injured heart is constructed.Methods In this study, we engineered mesoporous silica nanoparticles (MSNs) coated with a neutrophil membrane to act as a drug delivery system, encapsulating AL. The potential of the nanoparticles (named AL@MSNs@NM) for specific targeting of infarcted myocardium was assessed using small animal vivo imaging system. The cardiac function of AL@MSNs@NM after treatment was evaluated by Animal Ultrasound Imaging system, HE staining, and Laser Speckle Imaging System. The therapeutic mechanism was analyzed by ELISA kits, immunofluorescence, and PCR.Results We discovered that AL@MSNs@NM significantly improves cardiac function index, reduced infarct size and fibrosis, increased vascular perfusion in ischemic areas, and also promoted the function of CMECs, including migration, tube formation, shear stress adaptation, and nitric oxide production. Further research revealed that AL@MSNs@NM have cardio-protective functions in IR rats by inhibiting CMEC ferroptosis and increasing platelet endothelial cell adhesion molecule-1 (PECAM-1) expression.Conclusion Our results indicated that AL@MSNs@NM significantly reversed CMEC ferroptosis and increased PECAM-1 expression, enhanced cardiac function, and reduced myocardial infarction size. Therefore, this strategy demonstrates that engineered biomimetic nanotechnology effectively delivers AL for targeted therapy of myocardial infarction.
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ACS Applied Materials & Interfaces
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2024
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IF 8.3
Yuanyuan Wen,Kaiming Li,Mengnan Ni,Hui Jiang,Haisi Wu,Qinqi Yu,Jinyu Li,Xiaolin Li,Jifu Wei,Wei Wu,Huae Xu
Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8+ T cells and IFN-γ+ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.
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CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Fan Zhao,Hongyan Yu,Chen Wang,Junchen Xu,Hao Gao,Yao Ying,Wangchang Li,Juan Li,Jingwu Zheng,Liang Qiao,Shenglei Che,Jing Yu
Cuproptosis, ferroptosis, and reactive oxygen species (ROS)-involved apoptosis are all bound by the overexpressed glutathione (GSH) in tumor microenvironment (TME). Herein, a dual GSH depletor is developed based on copper/iron bimetal gallic acid phenolic networks (CuFeGA MPNs) for combination tumor therapy by GSH depletion boosted apoptosis/ferroptosis/cuproptosis simultaneously. The CuFeGA MPNs are dissociated following exposure to the highly expressed GSH, causing the release of large quantities of GA, Fe 2+ , and Cu + . The released GA then further consumes the residual GSH. In conjunction with the GSH response-consumption behavior, the GSH depletion is achieved by those dual GSH consumption procedures. Subsequently, the expression of glutathione peroxides 4 (GPX4) is down-regulated by GSH depletion for further accumulation of lipid peroxides (LPO). Moreover, intracellular ROS levels are improved via Fenton reaction with released Cu + and Fe 2+ , leading to buildup of LPO concurrently. Eventually, excess ROS can activate mitochondria-associated apoptosis, and the surge of LPO initiates ferroptosis without GSH homeostasis. Meanwhile, the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and decline of iron-sulfur cluster protein are induced by excessive Cu + in the absence of GSH chelation, activating cuproptosis. This work provides a feasible approach for the realization of multiple mechanisms combined tumor therapy.
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Advanced Healthcare Materials
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2024
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IF 10
Yuliang Xu,Sihan Wang,Jincheng Xiong,Pimiao Zheng,Huixia Zhang,Shiqi Chen,Qiang Ma,Jianzhong Shen,Tony Velkov,Chongshan Dai,Haiyang Jiang
Metal-organic framework (MOF)-based drug delivery nanomaterials for cancer therapy have attracted increasing attention in recent years. Here, we propose an enhanced chemodynamic anti-tumor therapy strategy by promoting the Fenton reaction by using core-shell zeolitic imidazolate framework-8 (ZIF-8)@Fe 3 O 4 as a therapeutic platform. Carboxymethyl cellulose (CMC) was used as a stabilizer of Fe 3 O 4 , which then decorated on the surface of ZIF-8 via the electrostatic interaction and served as an efficient Fenton reaction trigger. Meanwhile, the pH-responsive ZIF-8 scaffold acted as a container to encapsulate the chemotherapeutic drug doxorubicin (DOX). The obtained DOX-ZIF-8@Fe 3 O 4 /CMC nanoparticles concomitantly accelerated DOX release and generated more hydroxyl radicals by targeting the lysosomes in cancer cells. In vitro and in vivo studies verify that the DZFC nanoparticles trigger GPX4-dependent ferroptosis via the activation of the c-Jun N-terminal kinases (JNK) signaling pathway, following to achieve the chemo/ferroptosis synergistic anti-tumor efficacy. No marked toxic effects were detected during DZFC treatment in a tumor-bearing mouse model. This composite nanoparticle remarkably suppressed the tumor growth with minimized systemic toxicity, opening new horizons for the next generation of theragnostic nanomedicines. This article is protected by copyright. All rights reserved
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ADVANCED MATERIALS
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2025
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IF 26.8
Siyi Li,Jiaoting E,Xiucheng Zhao,Rui Xie,Jiaming Wu,Lili Feng,He Ding,Fei He,Piaoping Yang
Reactive oxygen species (ROS) play crucial roles in cellular metabolic processes by acting as primary intracellular chemical substrates and secondary messengers for cellular signal modulation. However, the artificial engineering of nanozymes to generate ROS is restricted by their low catalytic efficiency, high toxicity, and off-target consumption. Herein, hetero-trimetallic atom catalysts (TACs) anchored on a stable symmetrical pyramid structure are designed in the presence of N and P surface ligands from cross-linked polyphosphazene interlayer-coated MIL-101(Fe). The 3D network TACs with a uniform dispersion of Cu, Co, and Fe hetero-single atoms effectively tailor the active sites to avoid metal sintering, thereby providing sufficient catalytic activity for ROS blooms. Nanovesicle membranes facilitate the stable accumulation of nanozymes with homologous targeting, recognition, and endocytosis, effectively addressing the potentially high toxicity and off-target defects. Therefore, the outcome of the in situ ROS-bloom acts as a redox signal for directly regulating oxidative stress in the tumor microenvironment. Meanwhile, ROS intervene in the glutathione peroxidase 4, long-chain acyl-CoA synthetase 4, and cysteinyl aspartate specific proteinase-3 pathways as second messengers, fostering the proclivity toward apoptosis and lipid peroxidation-regulated ferroptosis pathway concurrently, thereby highlighting the application prospects of TACs in the biomedical field.
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Qiang-Ming Li,Shu-Zhen Wu,Xue-Qiang Zha,Dan-Dan Zang,Feng-Yun Zhang,Jian-Ping Luo
Ethnopharmacological relevance Ganoderma lucidum , a renowned tonic traditional Chinese medicine, is widely recognized for the exceptional activity in soothing nerves and nourishing the brain. It has been extensively employed to alleviate various neurological disorders, notably Parkinson’s disease (PD). Aim of the study To appraise the antiparkinsonian effect of GAA, the main bioactive constituent of G. lucidum, and clarify the molecular mechanism through the perspective of ferritinophagy-mediated dopaminergic neuron ferroptosis. Materials and methods PD mouse and cell models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP + ), respectively. Cell viability, behavioral tests and immunofluorescence analysis were performed to evaluate the neurotoxicity, motor dysfunction and dopaminergic loss, respectively. Biochemical assay kits were used to determine the levels of iron, lipid reactive oxygen species (ROS), malondialdehyde (MDA), total ROS and glutathione (GSH). Western blot and immunofluorescence were applied to detect the expressions of nuclear receptor co-activator 4 (NCOA4), ferritin heavy chain 1 (FTH1), p62 and LC3B. Additionally, NCOA4-overexpressing plasmid vector was constructed to verify the inhibitory effect of GAA on the neurotoxicity and ferroptosis-related parameters in PD models. Results GAA significantly mitigated MPP + /MPTP-induced neurotoxicity, motor dysfunction and dopaminergic neuron loss ( p ＜0.01 or p ＜0.05). In contrast to MPP + /MPTP treatment, GAA treatment decreased the levels of iron, MDA, lipid and total ROS, while increasing the GSH level. GAA also reduced the levels of NCOA4 and LC3B, and enhanced the expressions of FTH1 and p62 in PD models ( p ＜0.01 or p ＜0.05). However, the protective effect of GAA against the neurotoxicity, NCOA4-mediated ferritinophagy and ferroptosis in PD model was abolished by the overexpression of NCOA4 ( p ＜0.01). Conclusion GAA exerted a protective effect on PD, and this effect was achieved by suppressing dopaminergic neuron ferroptosis through the inhibition of NCOA4-mediated ferritinophagy.
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ULTRASONICS SONOCHEMISTRY
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2024
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IF 8.7
Jinyue Sun,Qian-Jun Shen,Jia-Neng Pan,Xiaodong Zheng,Ting Yu,Wen-Wen Zhou
The purpose of this study was to investigate ferroptosis in Escherichia coli O157:H7 caused by ferrous sulfate (FeSO 4 ) and to examine the synergistic effectiveness of FeSO 4 combined with ultrasound-emulsified cinnamaldehyde nanoemulsion (CALNO) on inactivation of E. coli O157:H7 in vitro and in vivo . The results showed that FeSO 4 could cause ferroptosis in E. coli O157:H7 via generating reactive oxygen species (ROS) and exacerbating lipid peroxidation. In addition, the results indicated that FeSO 4 combined with CALNO had synergistic bactericidal effect against E. coli O157:H7 and the combined treatment could lead considerable nucleic acids and protein to release by damaging the cell membrane of E. coli O157:H7. Besides, FeSO 4 combined with CALNO had a strong antibiofilm ability to inhibit E. coli O157:H7 biofilm formation by reducing the expression of genes related on biofilm formation. Finally, FeSO 4 combined with CALNO exhibited the significant antibacterial activity against E. coli O157:H7 in hami melon and cherry tomato.
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EUROPEAN POLYMER JOURNAL
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2024
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IF 5.8
Sihan Shen,Ran Xie,Yiqun Wang,Lingyu Jia,Zhangran Zhu,Hai Ma,Lifang Wang,Feng Sui,Yu Zhao,Qinghe Zhao,Yanjun Chen
Ferroptosis represents a novel procedure of programmed cell death driven by iron-dependent lipid peroxidation, and may offer a promising strategy for cancer therapy. In this study, we developed poly (2-ethyl-2-oxazoline)-poly (lactic acid)-SS-poly (β-amino ester) (PEOz-PLA-SS-PBAE) loaded with β-elemene. The disulfide bond mediated depletion of glutathione (GSH) and inactivation of glutathione peroxidase 4 (GPX4) will lead to inactivation of the antioxidant system of the tumor cell, and β-elemene has the capacity to generate reactive oxygen species (ROS), and the above changes would induce a disruption of the redox balance within the tumor cell, resulting in ferroptosis of the tumor cell. In conclusion, in this study, water insoluble β-elemene was solubilized by the triblock copolymer to construct a pH/GSH dual-responsive nano-delivery system, and combined with iron death and chemotherapy to exert combinatory inhibition effect on breast cancer cells, which provides a new idea for the potential clinical application of β-elemene
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