JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
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IF 9.7
Fang Wang,Ke Wang,BaoRu Fang,SiQi Geng,Ying Li,HuiFeng Qian,YiNuo Lin,ZhangSen Yu
Doxorubicin-induced cardiomyopathy (DIC) is a toxic side effect that cannot be ignored during chemotherapy for malignant tumors. In this work, we synthesized a novel nano-chemotherapeutic drug based on Prussian blue nanozyme to alleviate DIC. Hollow mesoporous Prussian blue (HmPB) nanoparticles were used as a carrier to load doxorubicin (DOX) through electrostatic adsorption and obtain a novel chemotherapy drug, HmPB(DOX). I n vivo and in vitro chemotherapy efficacy and acute toxicity evaluation experiments were conducted. The results suggest that HmPB(DOX) exhibits pH-responsive characteristics and minimizes the release of DOX from within HmPB(DOX) in cardiomyocytes. However, in the acidic tumor microenvironment, the release of DOX from HmPB(DOX) is notably enhanced. More importantly, HmPB(DOX) possesses excellent antioxidant enzyme activity, effectively clearing DOX-induced reactive oxygen species (ROS) and alleviating oxidative stress in cardiomyocytes. Doxorubicin is pivotal in the chemotherapy of malignant tumors. This study presents novel insights for mitigating the toxic and side effects of DOX, offering new strategies to enhance tolerance to chemotherapy.
研究领域:
药理学
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2025
·
IF 5.5
Jingchao Li,Yinghua Zeng,Fengjiao Liu,Xu Liao,Chongbin Zhong,Shujuan Dong,Yanbin Cai,Pingzhen Yang
Doxorubicin (DOX) chemotherapy is a cornerstone of cancer treatment, but its clinical application and effectiveness are severely restricted due to its life-threatening cardiotoxicity. Xanthohumol (XH), a compound from traditional Chinese medicine, is noted for its antioxidant properties and the potential to mitigate DOX-induced cardiotoxicity (DIC). However, its poor water solubility results in low biocompatibility, making it susceptible to immune system clearance, which severely restricts its application in vivo. In this study, we first identified and demonstrated that XH can effectively mitigate DIC by inhibiting ferroptosis. We designed a biomimetic nanodelivery system encapsulating XH within porous poly(lactic-co-glycolic acid) (PLGA) nanoparticles, further coated with an erythrocyte membrane (XH-NPs@RBCm). This system offers several advantages, including evasion of macrophage phagocytosis and prolonged circulation time, thereby enhancing the stability and bioavailability of XH in vivo. Treatment with XH-NPs@RBCm significantly reduced reactive oxygen species-dependent ferroptosis, improving the DOX-induced myocardial atrophy and cardiac dysfunction. Our study underscores the therapeutic promise of XH-NPs@RBCm in treating DIC through ferroptosis inhibition, offering key insights into biomimetic nanodelivery system development for DIC management.
研究领域:
药理学
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心血管病学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
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IF 10
Sitian Liu,Zihan Wang,Xinyi Chen,Mingying Han,Jie Xu,Ting Li,Liu Yu,Maoyu Qin,Meng Long,Mingchuan Li,Hongwu Zhang,Yanbing Li,Ling Wang,Wenhua Huang,Yaobin Wu
Cardiac safety assessments are significant in drug discovery, as drug-induced cardiotoxicity (DIC) is the primary cause of drug attrition. Despite heart-on-a-chip (HoC) technology becoming an increasingly popular tool for evaluating DIC, its development remains a challenge owing to the anisotropic cardiac structure of the native myocardium. Herein, an anisotropic multiscale cardiac scaffold is presented via a hybrid biofabrication method by combining 3D printing with electrospinning technology, where the 3D-printed micrometer-scale scaffold frames enable mimicking the interwoven myocardium anatomical structure and the branched-aligned electrospun nanofibers network is able to directionally guide cellular arrangements. The in vitro 3D bioengineered cardiac tissues are then fabricated by encapsulating three-layer multiscale scaffolds within a photocurable methacrylated gelatin hydrogel shell. It is demonstrated that such an anisotropic multiscale structure could contribute to enhancing cardiomyocyte maturation and synchronous beating behavior. More attractively, with the integration of 3D bioengineered cardiac tissues and a self-designed microfluidic perfusion system, a 3D anisotropic HoC platform is established for evaluating DIC and cardioprotective efficacy. Collectively, these results indicate that the HoC model developed by integrating the 3D bioengineered cardiac tissues could effectively recapitulate the clinical manifestations, thereby highlighting their efficacy as a valuable preclinical platform for testing drug efficacy and cardiotoxicity.
研究领域:
生物医学工程
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药理学
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组织工程
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
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IF 13.2
Binke Wang,Xinyu Qi,Ruping Yang,Xu Xu,Shiyao Li,Chunli Zhang,Haitao Yu
Liver cancer is one of the most prevalent and deadly malignancies worldwide, with limited effective therapeutic strategies. Although doxorubicin (DOX) is widely used as a frontline chemotherapeutic agent, its severe cardiotoxicity and lack of tumor selectivity significantly limited its clinical applications. Polydatin (PLD), a natural antioxidant and anticancer compound, has shown promise as an adjuvant for reducing DOX-induced cardiotoxicity, yet its poor bioavailability hinders its therapeutic potential. To improve the therapeutic efficacy of DOX while reducing systemic toxicity, we developed a hyaluronic acid (HA)-functionalized cubosome-based nanosystem co-loaded with DOX and PLD (1:3 ratio), i.e. HA 3% -D/P-CUBS + , to specifically target tumor sites with enhanced antitumor efficiency and alleviated DOX-induced cardiotoxicity. HA 3% -D/P-CUBS + significantly improved drug internalization and induced apoptosis in hepatocellular carcinoma cells (HepG-2 and HUH-7). Meanwhile, HA 3% -D/P-CUBS + protected normal hepatocytes (HL-7702 and AML-12) and reduced oxidative stress in cardiomyocytes (H9C2 cells). Notably, HA 3% -D/P-CUBS + inhibited in vivo tumor growth of 94 % without causing damage to vital organs, leading to improved survival rates. Moreover, it also mitigated DOX-induced oxidative stress by restoring the balance between oxidative and antioxidant systems. These findings highlight HA 3% -D/P-CUBS + as a promising and synergistic nanomedicine for targeted live cancer therapy, providing new insights into combination chemotherapy with enhanced safety and efficacy.
研究领域:
肿瘤学
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纳米医学
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药剂学
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分子药理学
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转化医学
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氧化应激
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产品关联
DOI
高影响因子
REDOX REPORT
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2025
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IF 7.4
Fang Cheng,Minzhu Zhao,Qi Wang,Hongli Xiong,Kai Yu,Chong Chen,Ying Zhu,Yemiao Chen,Jianbo Li
Objectives Doxorubicin (DOX) induces dose-dependent cardiotoxicity, primarily through oxidative stress and metabolic dysregulation. Although NAD+ deficiency has been implicated in cardiovascular pathology, its role in DOX-induced cardiotoxicity (DIC) remains poorly understood. This study investigated NAD+ metabolism dysregulation as a redox-sensitive mechanism in DIC pathogenesis.Methods Human cardiomyocytes (AC16), mouse atrial myocytes (HL-1), and C57BL/6 mice were used to establish the DIC model. The role and mechanism of NAD+ in DIC were investigated using a range of methods.Results Using integrated in vitro and in vivo models, we demonstrated that DOX induces myocardial oxidative damage accompanied by NAD+ depletion. Exogenous NAD+ supplementation mitigated the DOX-induced cardiomyocyte death and redox imbalance. Mechanistically, pharmacological CD38 inhibition with 78C or genetic silencing failed to restore the NAD+ pool, whereas nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3) overexpression, combined with nicotinamide mononucleotide (NMN) administration, effectively rescued NAD+ levels and attenuated oxidative stress. Computational and functional analyses identified FOXO1 as a transcriptional repressor of NMNAT3 following DOX exposure.Conclusion This study establishes the dysregulation of the FOXO1-NMNAT3 axis as a key mechanism underlying NAD+ depletion in DIC. Targeting this axis through NAD+ replenishment, particularly by activating NMNAT3, offers a novel redox-based therapeutic strategy against DIC.
研究领域:
心血管病理学
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分子生物学
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药理学
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氧化应激
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代谢调控
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转化医学
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药物毒性
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
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IF 10.7
Shuiling Qin,Zhiwei Wen,Huajie Huang,Wei Wu
Our research aimed to enhance the oral bioavailability of doxorubicin hydrochloride (DOX·HCl) while minimizing the potential for myocardial toxicity. To achieve this goal, we developed a new method that utilizes a coating material to encapsulate the drug in liposomes, which can specifically target intestinal taurine transporter proteins. This coating material, TAU-CS, was created by combining taurine with chitosan. We characterized TAU-CS using various methods, including 1 H NMR, FT-IR, and scanning electron microscopy (SEM). The resulting liposomes exhibited a regular spherical morphology, with a particle size of 195.7 nm, an encapsulation efficiency of 91.23 %, and a zeta potential of +11.65 mV. Under simulated gastrointestinal conditions, TAU-CS/LIP@DOX·HCl exhibited good stability and slow release. Pharmacokinetic studies revealed that, compared with DOX·HCl, TAU-CS/LIP@DOX·HCl had a relative bioavailability of 342 %. Intracellular uptake, immunofluorescence imaging, and permeation assays confirmed that the taurine transporter protein mediates the intestinal uptake of these liposomes. Our study suggested that liposomes coated with TAU-CS could serve as an effective oral delivery system and that targeting the taurine transporter protein shows promise in enhancing drug absorption.
研究领域:
药学
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药物递送系统
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药理学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2025
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IF 20.3
Zekun Wang,Ruofei Zhang,Yanyu Hu,Qile Song,Xiaoyan Fu,Yifan Wang,Mei Chen,Kelong Fan,Cundong Fan,Dongdong Sun
Doxorubicin (DOX) treatment can lead to intracellular iron overload in cardiomyocytes, triggering excessive generation of reactive oxygen species (ROS) and resulting in cardiotoxicity. Superoxide dismutase (SOD) effectively scavenges ROS, and its catalytic activity depends on the binding of metal ions at its active site. Therefore, enhancing the activity of metal-dependent SOD represents a promising strategy to inhibit ferroptosis in cardiomyocytes and alleviate DOX-induced chronic heart failure. In this study, we constructed a biomimetic chiral MnO 2 nanozyme co-modified with macrophage and platelet membranes (D/L-MnO 2 @MM), enabling precise targeting of DOX-injured myocardial tissues. This nanozyme exhibited potent catalase-like and SOD-like activities, efficiently eliminating excessive local hydrogen peroxide (H 2 O 2 ) and superoxide anions (O 2 •− ). Notably, the D-enantiomeric nanozyme (D-MnO 2 @MM) significantly enhanced endogenous SOD2 activity via Mn 2+ ion release, thereby suppressing the accumulation of lipid peroxides. Furthermore, based on transcriptomic and proteomic analyses, we designed an siRNA targeting the Hmox1 gene (si Hmox1 ) and successfully loaded it onto the nanozyme platform (si Hmox1 @D/L-MnO 2 @MM). Both in vitro and in vivo experiments confirmed that the dual mechanism, SOD2 activation and Hmox1 silencing, effectively restored mitochondrial function, attenuated ferroptosis, and significantly improved cardiac function in a rat model of chronic heart failure. Collectively, this study proposes a novel ferroptosis-targeted therapeutic strategy based on a biomimetic chiral nanozyme, offering new insights and promising therapeutic potential for the treatment of DOX-induced cardiotoxicity.
研究领域:
心血管病学
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纳米医学
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分子生物学
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药理学
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氧化应激
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基因治疗
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转化医学
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DOI
PubMed
高影响因子
Nano Research
·
2021
·Vol. 14
·期 11
·3988-3998
·
IF 8.897
He Jiaqi,Chen Guoqin,Zhao Peng,Ou Caiwen
Bufalin is efficacious in treating various tumors, however, the clinical application of which is restricted by the myocardial toxicity. Developing a smart synergetic delivery system is widely considered as a promising therapeutic strategy. To address this issue, a black phosphorus hybrid polypeptides hydrogel was designed to highly load bufalin, and achieved near-infrared (NIR)-controllable drug release with synergistic photothermal-chemo therapeutic effect. Black phosphorus nanosheets (BPNSs) and bufalin were co-loaded in temperature-sensitive supramolecular hydrogel to receive smart hybridization (BP-bufalin@SH). With NIR irradiation (1 W·cm −2 ), BP-bufalin@SH exhibited a rapid and large temperature increase and released bufalin via light-controllable manner, with which the side effects of bufalin were greatly decreased. Combined with photothermal-chemo therapeutic effect, BP-bufalin@SH could collapse the mitochondrial transmembrane potential resulting in the irreversible apoptosis of tumor cells, and realize a highly efficient in vivo tumor elimination with good biosafety and biocompatibility. This work provides a new hydrogel platform for controlling bufalin release, and thus further promotes the practical application on antitumor therapy.
研究领域:
药学
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纳米技术
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癌症治疗
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材料科学
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产品关联
DOI
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2024
·
IF 3.3
Liyuan Zhao,Lei Shi,Zixuan Yang,Minhui Zheng,Zhimin Sun,Luyao Sun,Mengyun Gu,Xin Song,Gang Liu,Feng Miao,Ming Wang,Shaoqiu Zheng,Peng Zhang,Naping Tang,Kelan Liu
Isoprenaline hydrochloride (IH) is a β-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague–Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity.
研究领域:
心脏病学
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分子生物学
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药理学
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毒理学
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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）