INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
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IF 5.2
Jianan Zhang,Yangli He,Yundi Wu,Tian Xie,Wanmeng Fu,Xilong Wu,Lei Zhou,Min Zeng
Effective management of myocardial ischemia/reperfusion (I/R) injury remains a clinical challenge. Epigallocatechin gallate (EGCG), a natural antioxidant, exhibits therapeutic potential in I/R models; however, it is limited by poor bioavailability and inadequate targeted delivery. Therefore, using a synergistic therapeutic strategy, we designed a nanoplatform (PB@PEI@FPBA-EGCG NPs, referred to as PPFE NPs) to address these limitations. PPFE NPs integrate Prussian blue nanoparticles (PB NPs) with EGCG, harnessing the multi-enzyme–mimicking activities of PB NPs (SOD/CAT mimetic, •OH scavenging) together with the pharmacological properties of EGCG. Notably, in this nanoplatform, PB NPs and EGCG demonstrate excellent synergistic therapeutic effects, characterized by enhanced ROS-responsive drug release and injured cardiac tissue-selected delivery. In vitro and in vivo studies confirmed the efficacy of PPFE NPs in neutralizing ROS, restoring mitochondrial homeostasis, and inhibiting apoptosis following I/R injury. Mechanistically, cardioprotection was mediated through the regulation of DJ-1 (PARK7) and its downstream pathways—Nrf2/ARE antioxidant signaling and ASK1/p38/JNK apoptotic regulation. Importantly, this study is the first to utilize native PB NPs as an EGCG carrier, exploiting their ROS scavenging ability and boronate ester bonds to improve EGCG loading efficiency and targeted delivery. Furthermore, we innovatively found that the combination of EGCG and DJ-1 may represent a key mechanism underlying the protective effects of EGCG against myocardial ischemia/reperfusion injury (MIRI). This work pioneers a ROS-responsive Prussian blue (PB) nanoplatform with superior synergistic efficacy. The study establishes PPFE NPs as a biocompatible nano-platform for myocardial I/R injury and provides a translatable strategy to optimize the clinical application of EGCG.
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
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IF 4.7
Wenying Fu,Ying Yan,Chongchong Shu,Chenxin Xu,Yinghua Chen,Yiqun Xia,Jundixia Chen,Yunzhi Chen,Ri Cui,Peng Zou,Daoyong Ni
6-Methoxydihydrosanguinarine is a natural alkaloid derived from medicinal plants that exhibits significant antitumor activity, making it a promising candidate for cancer therapy. However, the exact molecular mechanisms underlying its effects require further investigation. In this study, we investigated the cytotoxicity and underlying mechanisms of 6-Methoxydihydrosanguinarine in human non-small cell lung cancer (NSCLC) cells. Our findings reveal that reactive oxygen species (ROS) accumulation is the key driver of its antitumor activity. Mechanistically, 6-Methoxydihydrosanguinarine activates the JNK signaling pathway and induces endoplasmic reticulum (ER) stress, both of which can be reversed by the ROS scavenger N-acetylcysteine (NAC). Interestingly, 6-Methoxydihydrosanguinarine also activates autophagy, and inhibition of autophagy reverses the JNK and ER stress pathway activation induced by 6-Methoxydihydrosanguinarine. Notably, 6-Methoxydihydrosanguinarine synergistically enhances cisplatin-induced NSCLC cell death, and this synergistic effect is abolished by NAC, highlighting the critical role of ROS accumulation in their combined efficacy. This study systematically elucidates the molecular mechanisms of 6-Methoxydihydrosanguinarine against NSCLC, revealing that, in addition to the JNK and autophagy pathways, ER stress also mediates its antitumor effects. Moreover, our data establish a rationale for exploring 6-Methoxydihydrosanguinarine in NSCLC therapy and highlight its combination with cisplatin as a potentially effective strategy.
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CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
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2026
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IF 4.7
Gao Yuxuan,Kong Qiyu,Wang Jun,Sun Fengwei,Liu Xinyu,Wang Deliang,Li Jiangao,Yang Zhen
Developing organic type I photosensitizers (PSs) that generate less oxygen-dependent reactive oxygen species (ROS) has long been recognized to be an appealing yet significantly challenging task in the field of photodynamic therapy (PDT), owing to the high oxygen dependency of conventional PDT, which impairs its overall therapeutic efficacy, particularly in hypoxic solid tumors. Herein, a molecular fluorination strategy to finely regulate PSs with bright near-infrared (NIR) fluorescence and superior type I ROS generation ability was exploited. Benefited from the improved donor-acceptor interaction, promoted intersystem crossing process, and increased spin-orbit coupling (SOC) constant, the optimal TIBT-5F simultaneously exhibits broad absorption with a larger molar extinction coefficient in the visible-light region, bright NIR fluorescence emission and stronger type I ROS generation efficiency, making TIBT-5F a promising candidate for precise NIR fluorescence-guided PDT. The as-prepared TIBT-5F nanoparticles (NPs) can quickly accumulate in the tumor site, effectively produce both type II and type I ROS and prominently suppress the tumor growth under a safe white light irradiation (40 mW/cm 2 ) with minimized systemic toxicity. This study thus offers a new insight into constructing advanced type I PSs for precise fluorescence imaging-guided tumor theranostics.
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Frontiers in Immunology
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2026
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IF 7
Jiquan Shen,Changjian Zhou,Xinggao Wang,Yuxuan Chen,Run Liu,Liang Hong,Weiping Ji,Bo Wang
BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe synovial inflammation, joint deformities, and progressive tissue destruction. Celastrol (Cel), a natural triterpenoid with anti-inflammatory and antioxidant activity, is a promising therapeutic candidate for RA; however, its application is limited by poor aqueous solubility, low bioavailability, and systemic toxicity.PurposeThis study aimed to develop folate-modified liposomes encapsulating Cel (FA-Cel-LPs) to improve its solubility, stability, and joint accumulation, and to evaluate their anti-inflammatory efficacy and associated molecular changes in LPS-activated RAW264.7 macrophages and collagen-induced arthritis (CIA) rats.MethodsFA-Cel-LPs were prepared by thin-film hydration followed by extrusion and characterized for particle size, morphology, polydispersity index (PDI), encapsulation efficiency (EE), and in vitro release behavior. In LPS-activated RAW264.7 cells, cellular uptake, intracellular ROS levels, NF-κB nuclear translocation, COX-2/iNOS expression, and cytokine secretion were evaluated. In CIA rats, therapeutic efficacy was assessed by paw swelling, arthritis scores, in vivo fluorescence imaging, MRI, histological analysis, and micro-CT-based bone parameters. Safety was evaluated using hemolysis, serum biochemical analysis, and organ histology.ResultsFA-Cel-LPs showed a mean particle size of 110.65 ± 1.24 nm, an EE of 84.67 ± 2.55%, a PDI of 0.230 ± 0.018, and a sustained release profile with pH-dependent differences in vitro. In RAW264.7 cells, folate-modified liposomes showed greater cellular uptake and were associated with reduced ROS levels, attenuated NF-κB activation, and decreased COX-2, iNOS, and pro-inflammatory cytokine expression, with low cytotoxicity. In CIA rats, in vivo imaging suggested greater accumulation of FA-Cel-LPs in inflamed joints. Compared with free Cel and Cel-LPs, FA-Cel-LPs more effectively reduced paw swelling and joint inflammation while attenuating bone erosion and preserving joint architecture. Serum ALT and AST levels in the FA-Cel-LPs group remained within physiological ranges and were significantly lower than those in the free Cel group. Organ histology showed no obvious treatment-related injury, suggesting acceptable preliminary safety.ConclusionFA-Cel-LPs improved the solubility, formulation stability, and apparent joint accumulation of Cel and enhanced its anti-inflammatory and bone-protective effects in experimental RA. These effects were associated with reduced ROS/NF-κB/COX-2-related inflammatory changes, suggesting FA-Cel-LPs may represent a promising liposomal strategy for RA.
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Pharmaceutics
·
2026
·Vol. 18
·期 9
·1115
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IF 6.9
Qian Chen,Hui Yang,Meili Pei,Yanxia Sun,Yubei Li,Sen Yu,Xiaofeng Yang
Background:The fibrous tumor extracellular matrix (ECM), driven by cancer-associated fibroblasts (CAFs), forms a physical barrier against drugs and immune cells, yet direct CAF elimination risks promoting metastasis.Methods:In this study, we developed a locally injectable hydrogel based on synergistic dynamic covalent crosslinking (imine and boronate ester bonds), enabling instant gelation, shear thinning, and dual-pH/ROS-responsive degradation. Two types of drug-loaded nanoparticles (NPs), coated with homotypic cell membranes, were incorporated into this hydrogel. In the acidic, reactive oxygen species (ROS)-rich tumor microenvironment (TME), the system responsively releases the antifibrotic drug SIS3 to reprogram CAFs while simultaneously delivering doxorubicin (DOX) specifically to tumor cells. Biological effects were evaluated in vitro using cell cultures and in vivo in mouse models.Results:This dynamic hydrogel-based co-delivery system effectively reprograms CAFs, reduces tumor mechanical stress, breaks the fibrotic barrier, and promotes the deep infiltration of chemotherapeutics and immune cells, thereby enhancing the efficacy of chemotherapy.Conclusions:This injectable pH/ROS-responsive dynamic covalent hydrogel, loaded with CAF- and cancer cell-targeting NPs, remodels the TME, enhances drug and immune cell penetration, and offers a promising biomaterial-based strategy for cervical cancer treatment.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Jiaqi Chen,Jiayue Zhao,Yibin Xu,Xianglin Fei,Shujie Xu,Binke Chen,Wenzi Wu,Jiachen Zhuang,Xiuan Zhan,Aikun Fu
Enteric Lactobacillus plays a crucial role in maintaining the intestinal barrier integrity. Lactobacillus reuteri , one of the most described probiotic species of Lactobacillus , has been shown to alleviate enteritis-associated intestinal mucosal damage by stimulating the expansion of intestinal stem cells (ISCs). However, the underlying ligand-protein interactions remain unexplored. Therefore, this study aimed to elucidate the specific molecular mechanisms by which L. reuteri and its metabolites govern ISC stemness. We employed broiler enteritis model and organoid culture to compare the probiotic effect of a wild-type (WT) L. reuteri strain and a reuterin-deficient isogenic mutant. Compared to the WT strain, the deficient strain exhibited an impaired ability to alleviate inflammation, restore the intestinal barrier, and stimulate ISC proliferation both in vivo and ex vivo, indicating that reuterin is the essential effector. Furthermore, bioorthogonal click chemistry combined with in silico molecular docking were utilized to map the direct host protein targets. We identified protein disulfide-isomerase 1 (PDIA1), an endoplasmic reticulum (ER)-resident redox-active protein, as the direct binding partner of reuterin, characterized by a strong binding affinity. The inactivation of PDIA1 by reuterin binding increased ER-derived reactive oxygen species (ROS) level, leading to the upregulation of Wnt/β-catenin pathway and the maintenance of ISCs. In conclusion, by inactivating the ER-resident PDIA1, L. reuteri -derived reuterin promoted ISC proliferation and ameliorated intestinal mucosal damage.
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ACS Applied Materials & Interfaces
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2023
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IF 9.5
Yibing Li,Ling Lin,Jiashan Xie,Lixue Wei,Shuping Xiong,Kunyi Yu,Bingchen Zhang,Shengtao Wang,Zibo Li,Yan Tang,Guimei Chen,Zhongjun Li,Zhiqiang Yu,Xuefeng Wang
The hypopermeability and hypoxia in the tumor milieu are important factors that limit multiple treatments. Herein, the reactive oxygen species (ROS)-triggered self-assembled nanoparticles (RP-NPs) was constructed. The natural small molecule Rhein (Rh) was encapsulated into RP-NPs as a sonosensitizer highly accumulated at the tumor site. Then highly tissue-permeable ultrasound (US) irradiation induced apoptosis of tumor cells through the excitation of Rh and acoustic cavitation, which prompted the rapid production of large amounts of ROS in the hypoxic tumor microenvironment. In addition, the thioketal bond structures in the innovatively designed prodrug LA-GEM were triggered and broken by ROS to achieve rapid targeted release of the gemcitabine (GEM). Sonodynamic therapy (SDT) increased the tissue permeability of solid tumors and actively disrupted redox homeostasis via mitochondrial pathways to kill hypoxic tumor cells, and the triggered response mechanism to GEM synergistically amplified the effect of chemotherapy. The chemo-sonodynamic combinational treatment approach is highly effective and noninvasive, with promising applications for hypoxic tumor elimination, such as in cervical cancer (CCa) patients who want to maintain their reproductive function.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 2
·1520
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IF 5.6
Shanshan Zhang,Dongliang Liu
The diverse application potential of metal-organic framework (MOF) materials are currently limited by their challenging and complicated preparation processes. In this study, we successfully developed a novel strategy for the rapid synthesis of a sustainable MOF composite membrane under neutral conditions with improved physicochemical and antibacterial properties. Our reaction pipeline comprised visible light that induced the production of reactive oxygen species (ROS) from ZIF-8 particles, which facilitated the rapid oxidative polymerization of dopamine to polydopamine. The physicochemical properties of the composite membrane were assessed using imaging methods, including scanning and transmission electron microscopy, X-ray photoelectron spectrometry, and nitrogen adsorption/desorption; its antibacterial effects againstStaphylococcus aureus,Escherichia coli, andPseudomonas aeruginosawere measured using optical densitometry. The bactericidal potency of the synthesized membrane was >99% against all tested strains under the conditions of simulated sunlight. Moreover, the composite membrane retained its structural integrity and antibacterial effect after multiple cycles of use and recovery, showcasing remarkable stability. Overall, this study displays a ROS-mediated method for the rapid preparation of sustainable MOF composite membranes under neutral conditions with optimal physicochemical characteristics, antibacterial properties, and performance. Our study provides insights into the use of membrane materials as design platforms for a range of diverse practical applications.Keywords:reactive oxygen species;visible light;dopamine polymerization;mild conditions;metal-organic framework;antibacterial membrane
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NANOTECHNOLOGY
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2022
·Vol. 33
·期 43
·435101
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IF 3.953
Meng Lan,Zhaodi Kong,Fengjie Liu,Tengteng Zou,Lihong Li,Tiange Cai,Huaqin Tian,Yu Cai
Abnormal apoptosis can lead to uncontrolled cell growth, aberrant homeostasis or the accumulation of mutations. Therapeutic agents that re-establish the normal functions of apoptotic signaling pathways offer an attractive strategy for the treatment of breast cancer. Baicalin (BA) is one of the natural compounds with anti-proliferation and pro-apoptosis activities against numerous tumor cells. However, low bioavailability restricts the clinical application of BA. In order to improve its therapeutic efficacy and study the mechanism of actions, active targeting delivery systems were developed for targeting tumor environment and selective cell killing effects. It emphasized on the construction of folate-conjugated albumin nanoparticles loaded with baicalin (FA-BSANPs/BA) and mechanisms of which on the promotion of breast cancer apoptosis. The physicochemical properties and structural characteristics of FA-BSANPs/BA were investigated. Cell experiments were carried out to study the targeted anti-breast cancer effects of FA-BSANPs/BA and its mechanism. The results showed that FA-BSANPs/BA was successfully constructed with stable structural characteristics and sustained release effects. Cellular uptake and MTT showed that it increased targeted uptake efficiency and cytotoxicity. Flow cytometry and western blot confirmed that it promoted apoptosis by increasing the expression of caspase-8 and ROS, and decreasing the level of Bid. It is suggested that the pro-apoptotic mechanism of FA-BSANPs/BA is related to regulation of key proteins in extrinsic apoptotic pathway. In conclusion, FA-BSANPs/BA is a good delivery carrier and significantly inhibits the breast cancer growth compared with free BA. The mechanism of FA-BSANPs/BA promoting apoptosis of breast cancer may be due to its action on the caspase-8/Bid/ROS pathway.
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Bioactive Materials
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2022
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IF 16.874
Lulu Jin,Zhixin Zhu,Liangjie Hong,Zhefeng Qian,Fang Wang,Zhengwei Mao
Ischemic stroke is an acute and serious cerebral vascular disease, which greatly affects people's health and brings huge economic burden to society. Microglia, as important innate immune components in central nervous system (CNS), are double-edged swords in the battle of nerve injury, considering their polarization between pro-inflammatory M1 or anti-inflammatory M2 phenotypes. High mobility group box 1 (HMGB1) is one of the potent pro-inflammatory mediators that promotes the M1 polarization of microglia. 18β-glycyrrhetinic acid (GA) is an effective intracellular inhibitor of HMGB1, but of poor water solubility and dose-dependent toxicity. To overcome the shortcomings of GA delivery and to improve the efficacy of cerebral ischemia therapy, herein, we designed reactive oxygen species (ROS) responsive polymer-drug conjugate nanoparticles (DGA) to manipulate microglia polarization by suppressing the translocation of nuclear HMGB1. DGA presented excellent therapeutic efficacy in stroke mice, as evidenced by the reduction of infarct volume, recovery of motor function, suppressed of M1 microglia activation and enhanced M2 activation, and induction of neurogenesis. Altogether, our work demonstrates a close association between HMGB1 and microglia polarization, suggesting potential strategies for coping with inflammatory microglia-related diseases.
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FOOD AND CHEMICAL TOXICOLOGY
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2022
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IF 5.572
Xiangyuan Liu,Li Song
Epidemiologic studies have revealed that Dichlorodiphenyltrichloroethane (DDT) and its metabolites are associated with liver diseases. However, there has been little emphasis on the mechanism underlying liver toxicity of o,p’- DDT and relevant effective inhibitors investigation. This study indicated o,p’- DDT exposure significantly decreased cell viability and promoted lactate dehydrogenase (LDH) release based on the investigation of cytotoxicity by trypan blue exclusion counts, MTT, and lactate dehydrogenase (LDH) assays. Comet, micronuclei, and DNA-protein crosslinks (DPC) assays demonstrated o,p’- DDT exposure increased the comet parameters, micronuclei frequency, and DPC coefficient. Meanwhile, we found o,p’- DDT induced mitochondria-dependent apoptosis , which is characterized by the loss of mitochondrial membrane potential (Δψm), decreased Bcl-2 expression, and increased protein levels of Bax, cytochrome c , activated-caspase-9, and activated-caspase-3. Furthermore, o,p’- DDT induced reactive oxygen species (ROS) overproduction, decreased the protein levels of nuclear factor erythroid-derived 2-like 2 (Nrf2) in the nuclear, and enhanced the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase . However, quercetin treatment significantly antagonized o,p’- DDT-induced cytotoxicity, genotoxicity , and apoptosis as well as effects on ROS, Nrf2, and NADPH oxidase. Taken together, these findings suggested quercetin could alleviate o,p’- DDT-induced toxicity in HL-7702 cells via inhibiting ROS production, which is modulated by down-regulating nuclear Nrf2 levels and NADPH oxidase expression.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
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IF 6.7
Jianv Wang,Jing Jia,Qingqing He,Yang Xu,Hongye Liao,Xia Xiong,Li Liu,Changzhen Sun
Recent advancements in tumour-targeted therapies and immunotherapy offer hope to patients with various malignancies. However, the uncontrolled growth and metastatic infiltration of malignant tumours remain a huge therapeutic challenge. Therefore, this study aimed to develop an integrated multifunctional diagnostic and treatment reagent IR-251 that can not only be used for tumour imaging but also to inhibit tumour growth and metastasis. Besides, our results showed that IR-251 targeted and damaged the mitochondria in cancer cells via organic anion-transporting polypeptides . Mechanistically, IR-251 induced ROS overproduction by inhibiting PPARγ and then inhibiting the β-catenin signalling pathway and downstream protein molecules related to the cell cycle and metastasis. Moreover, the excellent anti-tumour proliferation and metastasis ability of IR-251 were verified in vitro/in vivo . And histochemistry staining revealed that IR-251 inhibited tumour proliferation and metastasis, which showed no significant side effect. In conclusion, this novel, multifunctional, mitochondria-targeting near-infrared fluorophore probe IR-251 has great potential in achieving accurate tumour imaging and inhibiting tumour proliferation and metastasis, and the underlying mechanism of action of IR-251 is mainly via the PPARγ/ROS/β-catenin pathway.
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