Science of Advanced Materials
·
2015
·Vol. 7
·期 5
·855-860
·
IF 2.598
Yu Huijuan,Xi Chenbin,Hu Jianhua,Du Ming,Yang Dong
An amphiphilic copolymer, PEG-b-PLA-b-(PAA-co-PNIPAM), was synthesized via atom transfer radical polymerization of tert-butyl acrylate and N-isopropyl acryamide using PEG-b-PLA-Br as a macroinitiator and CuBr/Me6 TREN as a catalytic
system, followed by selectively hydrolyzing tert-butyl groups to carboxyl groups. Then, doxorubicin (DOX) was loaded to the hydrophobic core, and the PAA segments were cross-linked by cystamine to get disulfide cross-linked and DOX loaded micelles. The transmission electron microscopy
images showed that the cross-linked DOX loaded micelles were spherical nanoparticles, with a mean diameter of 100 nm. The drug release behavior of the cross-linked DOX loaded micelles was redox responsive. The cumulative release amount of DOX was 33.1% with the presence of 10 mM of glutathione
(GSH) at 37 °C, much higher than that without the presence of GSH, which was only 4.3%. Furthermore, the cumulative release amount of DOX was 50.9% at 25 °C, higher than that at 37 °C, indicating that the cross-linked DOX loaded micelles were also thermo-sensitive.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2020
·
IF 4.389
Zhoujiang Chen,Guanghui Hong,Zhiyan Liu,Dayun Yang,Ranjith Kumar Kankala,Wenguo Wu
Despite the success, the applicability of traditional chemotherapy still faces several challenges in treating cancer-related ailments, such as enormous toxicity and adverse effects. Combinatorial chemotherapy at reduced doses can offer augmented therapeutic efficiency through multiple mechanisms and even substantially circumvents the issues of toxicity and adverse effects. To demonstrate these facts, herein, two kinds of antitumor drugs, doxorubicin (DOX) and gambogic acid (GA), are encapsulated in bovine serum albumin (BSA) nanoparticles distinctly, resulting in DNP and GNP, respectively. These drug-loaded albumin nanocomposites, DNPs, and GNPs, showed a synergistic effect in ablating HepG2 tumor cells at a combination index (CI) of 0.38. Further, the ex vivo fluorescence imaging investigation confirmed the enriched drug internalization in the tumor precisely, which could be due to the enhanced permeation and retention (EPR) effect, resulting in the augmented therapeutic efficiency of designed nanoformulation. Notably, the synergistic tumor inhibition efficacy is more significantly attained at a 3-fold lesser dose of combined treatment than that of single full dose treatment in vivo . As anticipated, these conditions resulted in reduced organ toxicity. Together, this combinatorial strategy using BSA-based composites is an appropriate approach for application in medicine.
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Materials Science & Engineering C-Materials for Biological Applications
·
2016
·
IF 3.42
Ying Zhang,Xiang Wang,Yanli Su,Dongya Chen,Wenxing Zhong
Samarium (Sm) incorporated mesoporous bioactive glasses (MBG) microspheres have been prepared using the method of alginate cross-linking with Ca 2 + ions. The in vitro bioactivities of Sm/MBG/alginate microspheres were studied by immersing in simulated body fluid (SBF) for various periods. The results indicated that the Sm/MBG/alginate microspheres have a faster apatite formation rate on the surface. To investigate their delivery properties further, doxorubicin (DOX) was selected as a model drug. The results showed that the Sm/MBG/alginate microspheres exhibit sustained DOX delivery, and their release mechanism is controlled by Fickian diffusion according the Higuchi model. In addition, the delivery of DOX from Sm/MBG/alginate microspheres can be dominated by changing the doping concentration of Sm and the values of pH microenvironment. These all revealed that this material is a promising candidate for the therapy of bone cancer.
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FOOD AND CHEMICAL TOXICOLOGY
·
2025
·
IF 3.5
Nan Wang,Zhengshan Gao,Honghong Zhan,Lin Jing,Fancheng Meng,Min Chen
Doxorubicin (DOX) is a potent anticancer drug, while its toxic side effects involve multi-organ toxicity, including hepatotoxicity. This study aims to investigate the therapeutic potential of salidroside against DOX-induced hepatotoxicity and elucidate its underlying mechanisms. Result showed that salidroside exhibited a liver protective effect in DOX-induced hepatotoxicity in mice, represented by the decreased serum ALT, AST and LDH levels, as well as the rescue of pathological changes in mice livers. Further study showed salidroside reduced the expression level of pyroptosis-associated proteins, including NLRP3, cleaved- caspase 1, gasdermin D (GSDMD-N) and mature IL-1β in mice liver tissues. In vitro study confirmed salidroside exerted a similar effect in AML12 cells. Mechanistically, salidroside alleviated mitochondrial dysfunction by activating the PGC-1α /Mfn2 signaling pathway, and restrained the endoplasmic reticulum (ER) stress, represented by the downregulation of GRP78 and p-PERK/PERK level. Subsequent investigations revealed that salidroside activated the Sestrin2/AMPK pathway, while the application of AMPK inhibitors, PGC-1α siRNA or Sestrain2 siRNA reversed the effects of salidroside on ameliorating mitochondrial dysfunction and ER stress, suggesting salidroside could be a promising therapeutic strategy for alleviating DOX-induced hepatotoxicity.
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MOLECULAR BIOLOGY REPORTS
·
2026
·Vol. 53
·期 1
·1291
·
IF 3.2
Zhu Mo-li,Hao Rui,Zhao Meng-yao,Liu Pei-yao,Zhang Hong-dou,Li Peng,Yin Ya-ling,Liu Hui-jun,Ren Guang-qiu,Zhang Jie,Yang Jing
Background The clinical use of doxorubicin (DOX), a widely used and effective antitumor drug, is limited by its cardiotoxicity. Currently, safe and effective strategies for preventing doxorubicin-induced cardiotoxicity (DIC) remain limited. Therefore, this study aimed to investigate the potential cardioprotective effects and possible underlying mechanisms of L-arginine (L-Arg) against DIC. Methods and Results To investigate the cardioprotective effects and underlying mechanisms of L-Arg, three complementary experimental models were used: male Sprague–Dawley rats ( n = 6 per group), male AMPKα2 knockout (AMPKα2 KO) mice ( n = 6 per group), and H9c2 cardiomyocytes. A DIC model was induced in rats by intraperitoneal injection of DOX (2.5 mg/kg/week) for 6 weeks. Serum nitric oxide (NO) and lactate dehydrogenase (LDH) levels were measured to assess oxidative stress and myocardial injury. Cardiac morphology, inflammation, and fibrosis were evaluated by histological staining and protein expression analyses, whereas miR-29b-3p expression was determined by RT-qPCR. AMPKα2-deficient models and miR-29b-3p gain- and loss-of-function models were used to investigate the underlying mechanisms. Compared with the DOX group, L-Arg significantly improved cardiac function and morphology, reduced oxidative stress, myocardial injury, inflammation, and fibrosis, and increased miR-29b-3p expression (all P < 0.05). Moreover, miR-29b-3p overexpression enhanced, whereas miR-29b-3p inhibition attenuated, the cardioprotective effects of L-Arg ( all P < 0.05 ). These protective effects were also markedly attenuated by AMPKα2 deficiency ( P < 0.05 ). Conclusions L-Arg alleviates DIC by improving cardiac function, reducing oxidative stress, inflammation, and fibrosis, and increasing miR-29b-3p expression. These cardioprotective effects are associated with AMPKα2 activation and enhanced miR-29b-3p expression.
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Nanomedicine
·
2026
·
IF 4.6
Yang Tan,Lin Wang,Yu Duan,Guangliang Huang,Xiaoyan Xie,Nan Zhang,Baoxian Liu
Aims Radiofrequency ablation (RFA) is a common treatment for malignant tumors, yet recurrence and metastasis persist a major challenge. The hypoxic microenvironment induced by RFA is a key driver of residual tumor aggressiveness and chemoresistance. This study aims to develop perfluoropentane-based doxorubicin-loaded nanodroplets (DOX-NDs) to overcome these limitations.Materials and methods DOX-NDs were synthesized via thin-film hydration and characterized for morphology, stability, and heat-responsive behavior. In vitro studies examined the mechanisms of hypoxia alleviation, epithelial-mesenchymal transition reversal, and P-glycoprotein downregulation. Antitumor efficacy and biodistribution were evaluated in a 4T1 murine breast cancer model.Results DOX-NDs exhibited uniform spherical morphology and efficient oxygen loading. Upon thermal stimulation (>42°C), a phase transition in the nanodroplets triggered the rapid co-release of doxorubicin and oxygen. This oxygen replenishment promoted HIF-1α degradation, which restored E-cadherin expression and downregulated P-glycoprotein, thereby inhibiting cell motility and reversing chemoresistance. In vivo, the combination of DOX-NDs and RFA significantly suppressed tumor growth and pulmonary metastasis while demonstrating a favorable safety profile.Conclusions Targeting the hypoxia-recurrence axis with an RFA-responsive nanoplatform is a viable strategy. The DOX-NDs successfully integrate chemotherapy with hypoxia modulation, presenting a potential means to improve outcomes following tumor ablation.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Shuoning Wu,Ting Wang,Zhijie Mao,Zhentong Yang,Zhuoqun Wang,Zhuyin Jia,Zhouqing Huang,Yonghua Wang
Purpose Doxorubicin (DOX), a widely used chemotherapeutic agent for malignancies, exhibits dose-dependent cardiotoxicity, which restricts its clinical utility. While artesunate (ART) demonstrates potentially cardioprotective effects against acute DOX-induced cardiac damage, its role in chronic cardiotoxicity and its underlying mechanisms remain unclear. This study aimed to elucidate the mechanism underlying artesunate-mediated protection against doxorubicin (DOX)-induced cardiotoxicity. Methods Mice were treated with 5 mg/kg DOX (intraperitoneal injection) once weekly for 4 weeks to induce myocardial damage and with 25 mg/kg ART (intragastric administration) for 28 days. Echocardiography and histological staining were used to evaluate cardiac function and structural changes. We also assessed mRNA and protein levels using real-time polymerase chain reaction and Western blotting, respectively, and evaluated HuR-Sirt1 mRNA interaction via RNA immunoprecipitation (RIP). Results ART treatment significantly ameliorated DOX-induced cardiac dysfunction, fibrosis, hypertrophy, and apoptosis both in vivo and in vitro . Furthermore, ART restored cardiac sirtuin-1 (Sirt1) expression, which was suppressed by DOX. Critically, cardiac-specific Sirt1 knockout exacerbated DOX-induced cardiac damage and abolished the protective effects of ART. Mechanistically, we observed that siRNA-mediated HuR knockdown reduced Sirt1 expression, whereas Sirt1 knockdown did not affect HuR expression, indicating that HuR positively regulates Sirt1 expression. ART promotes the nuclear-to-cytoplasmic translocation of HuR, thereby enhancing its binding to Sirt1 mRNA and stabilizing Sirt1 transcripts. Conclusion Collectively, these findings demonstrate that ART attenuates DOX cardiotoxicity by activating the HuR-Sirt1 axis through the stabilization of Sirt1 mRNA.
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Oncology Letters
·
2026
·Vol. 32
·期 1
·1-11
·
IF 2.1
Ningning Fan,Guanying Liang,Jiayue Shao,Qi Wang,Lu Fu
Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 8
·7023
·
IF 5.6
Xiaowen Han,Mingda Zhao,Ruiling Xu,Yaping Zou,Yuxiang Wang,Jie Liang,Qing Jiang,Yong Sun,Yujiang Fan,Xingdong Zhang
Lesioned tissue requires synchronous control of disease and regeneration progression after surgery. It is necessary to develop therapeutic and regenerative scaffolds. Here, hyaluronic acid (HA) was esterified with benzyl groups to prepare hyaluronic acid derivative (HA-Bn) nanofibers via electrospinning. Electrospun membranes with average fiber diameters of 407.64 ± 124.8 nm (H400), 642.3 ± 228.76 nm (H600), and 841.09 ± 236.86 nm (H800) were obtained by adjusting the spinning parameters. These fibrous membranes had good biocompatibility, among which the H400 group could promote the proliferation and spread of L929 cells. Using the postoperative treatment of malignant skin melanoma as an example, the anticancer drug doxorubicin (DOX) was encapsulated in nanofibers via hybrid electrospinning. The UV spectroscopy of DOX-loaded nanofibers (HA-DOX) revealed that DOX was successfully encapsulated, and there was a π–π interaction between aromatic DOX and HA-Bn. The drug release profile confirmed the sustained release of about 90%, achieved within 7 days. In vitro cell experiments proved that the HA-DOX nanofiber had a considerable inhibitory effect on B16F10 cells. Therefore, the HA-Bn electrospun membrane could facilitate the potential regeneration of injured skin tissues and be incorporated with drugs to achieve therapeutic effects, offering a powerful approach to developing therapeutic and regenerative biomaterial.Keywords:electrospinning;drug delivery;postoperative therapy
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MOLECULES
·
2022
·Vol. 27
·期 23
·8455
·
IF 4.927
Hongping Xu,Junhong Ling,Han Zhao,Xinyi Xu,Xiao-kun Ouyang,Xiaoyong Song
Chemotherapy is a common method for tumor treatment. However, the non-specific distribution of chemotherapeutic drugs causes the death of normal cells. Nanocarriers, particularly mesoporous carriers, can be modified to achieve targeted and controlled drug release. In this study, mesoporous polydopamine (MPDA) was used as a carrier for the antitumor drug doxorubicin (DOX). To enhance the release efficiency of DOX in the tumor microenvironment, which contains high concentrations of glutathione (GSH), we used N,N-bis(acryloyl)cysteamine as a cross-linking agent to encapsulate the surface of MPDA with fucoidan (FU), producing MPDA-DOX@FU-SS. MPDA-DOX@FU-SS was characterized via transmission electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS), and its antitumor efficacy in vitro was investigated. The optimal conditions for the preparation of MPDA were identified as pH 12 and 20 °C, and the optimal MPDA-to-FU ratio was 2:1. The DOX release rate reached 47.77% in an in vitro solution containing 10 mM GSH at pH 5.2. When combined with photothermal therapy, MPDA-DOX@FU-SS significantly inhibited the growth of HCT-116 cells. In conclusion, MPDA-DOX@FU-SS may serve as a novel, highly effective tumor suppressor that can achieve targeted drug release in the tumor microenvironment.Keywords:mesoporous polydopamine;antitumor;nanomedicine;photothermal synergistic chemotherapy
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CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Yaodong Yi,Hengbin Zhang,Mingyang Chen,Binxin Chen,Yingchun Chen,Ping Li,Hui Zhou,Zhiyuan Ma,Huidi Jiang
Doxorubicin (DOX) has been widely used to treat various tumors; however, DOX-induced cardiotoxicity limits its utilization. Since high accumulation of DOX in cardiomyocytes/mitochondria is the key reason, we aimed to clarify the mechanisms of DOX uptake and explore whether selectively inhibiting DOX uptake transporters would attenuate DOX accumulation and cardiotoxicity. Our results demonstrated that OCTN1/OCTN2/PMAT (organic cation/carnitine transporter 1/2 or plasma membrane monoamine transporter), especially OCTN2, played crucial roles in DOX uptake in cardiomyocytes, while OCTN2 and OCTN1 contributed to DOX transmembrane transport in mitochondria. Metformin (1–100 μM) concentration-dependently reduced DOX (5 μM for accumulation, 500 nM for cytotoxicity) concentration and toxicity in cardiomyocytes/mitochondria via inhibition of OCTN1-, OCTN2- and PMAT-mediated DOX uptake but did not affect its efflux. Furthermore, metformin ( iv : 250 and 500 mg/kg or ig : 50, 100 and 200 mg/kg) could dose-dependently reduce DOX (8 mg/kg) accumulation in mouse myocardium and attenuated its cardiotoxicity. In addition, metformin (1–100 μM) did not impair DOX efficacy in breast cancer or leukemia cells. In conclusion, our study clarified the role of multiple transporters, especially OCTN2, in DOX uptake in cardiomyocytes/mitochondria; metformin alleviated DOX-induced cardiotoxicity without compromising its antitumor efficacy by selective inhibition of multiple transporters mediated DOX accumulation in myocardium/mitochondria.
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Bioactive Materials
·
2022
·
IF 16.874
Sunfan Li,Fangzhou Li,Dong Wan,Zuqin Chen,Jie Pan,Xing-Jie Liang
Chemotherapy remains the mainstay of cancer treatment, benefiting millions of patients each year, but the side effects of chemotherapy drugs severely limit their clinical use. Doxorubicin (DOX) can cause various side effects such as heart damage and treatment-related tumors. The effective use of active and passive targeting will improve the clinical application of DOX. Here, TPGS 3350 and bioactive peptides were utilized to construct a micelle-based stage-by-stage impelled efficient system (missiles) for DOX delivery (DOX missiles). By taking advantage of the EPR effect, DOX missiles are efficiently enriched at the tumor site. After being cleaved by matrix metalloproteinase2 (MMP2), the peptide (VRGD) targets tumor cells to facilitate uptake of the missiles by the tumor cells via receptor-mediated endocytosis. The intracellular activated caspase-3-catalyzed explosion of DOX missiles further enables efficient tumor killing. This study provides an efficient approach for DOX delivery and toxicity reduction.
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