ADVANCES IN POLYMER TECHNOLOGY
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2025
·Vol. 2025
·期 1
·9396134
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IF 2.5
Ye Fan,Ming Lu,Junyi Huang,Ling Huang,Huade Zheng
Drug-eluting embolic microspheres are receiving increasing attention in transarterial chemoembolization (TACE), which is one of the most important approaches for the treatment of unresectable hepatocellular carcinoma (HCC). However, currently most commercial microspheres are radiolucent and their position in vivo needs to be indirectly monitored by X-ray angiography. In addition, microspheres reflux may cause nontargeted embolism. The aim of this study is to develop an inherently radiopaque embolic agent capable of delivering drugs and enhancing the embolic effect. In this study, using emulsification (S/W/O) and photocrosslinking, the mixture of methacrylated polyvinyl alcohol (PVAMA), 2-acrylamide-2-methylpropanesulfonic acid (AMPS), and barium sulfate was prepared into BaSO 4 /PVA/AMPS beads. Barium sulfate act as computed tomography (CT) contrast agent, while sulfonic acid groups give the hydrogel beads drug loading and sustained release properties. The embolic performance of beads is enhanced by loading etamsylate. The results indicate that the prepared beads are radiopaque, biocompatible, with good drug sustained release performance. In vivo embolization and imaging properties were demonstrated by a rabbit ear central artery embolization model.
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Frontiers in Pharmacology
·
2019
·
IF 3.845
Li Ke,Zhan Wenhua,Chen Yulong,Jha Rajiv Kumar,Chen Xueli
Combination chemotherapy has been proven to be an efficient strategy for the treatment of prostate cancer (PCA). However, the pharmacokinetic distinction between the relevant drugs is an insurmountable barrier to the realization of their synergistic use against cancer. To overcome the disadvantages of combination chemotherapy in the treatment of PCA, targeted nanoparticles (NPs), which can codeliver docetaxel (DOC) and doxorubicin (DOX) at optimal synergistic proportions, have been designed. In this study, the DOC and DOX codelivery nanoparticles (DDC NPs) were constructed by hyaluronic acid (HA) and cationic amphipathic starch (CSaSt) through a self-assembly process. Human PCA cell lines (PC-3, DU-145, and LNCap) and mouse models were then used for evaluation in vitro and in vivo, respectively, of delivery and antitumor effects. The DDC NPs were spherical with rough surfaces, and the size and zeta potential were 68.4 ± 7.1 nm and -22.8 ± 2.2 mV, respectively. The encapsulation efficiencies of DOC and DOX in the NPs were 96.1 ± 2.3% and 91.4 ± 3.7%, respectively, while the total drug loading was 9.1 ± 1.7%. Moreover, the ratio of DOC to DOX in the DDC NPs was approximately 1:400, which aligned with the optimal synergistic proportions of the drugs. The DDC NPs exhibited excellent loading capacities, performed sustained and enzymatic release, and were stable in PBS, medium, and serum. After investigations in vitro, the DDC NPs were as effective as the dual drug combination in terms of cytotoxicity, antimigration, and apoptosis. Internalization results indicated that the DDC NPs could effectively deliver and fully release the payloads into PCA cells, and the process was mediated by the ligand-receptor interaction of HA with the CD44 protein. Low toxicity in vivo was confirmed by acute toxicity and hemolytic assays. The distribution in vivo showed that DDC NPs could enhance the accumulation of drugs in tumors and decrease nonspecific accumulation in normal organs. More importantly, DDC NPs significantly promoted the curative effect of the DOC and DOX combination in the PCA cell xenograft mouse model, indicating that the drugs with NPs did indeed act synergistically. This study suggests that the DDC NPs possess noteworthy potential as prospects for the development of PCA clinical chemotherapy.
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CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Shulin Wang,Xuan Zhang,Yanhong Hou,Yuliang Zhang,Jiamin Chen,Shuhan Gao,Huiying Duan,Shaoju Gu,Shanshan Yu,Yi Cai
The Sirtuins family, formally known as the Silent Information Regulator Factors, constitutes a highly conserved group of histone deacetylases. Recent studies have illuminated SIRT6's role in doxorubicin (DOX)-induced oxidative stress and apoptosis within myocardial cells. Nevertheless, the extent of SIRT6's impact on DOX-triggered myocardial cell aging and damage remains uncertain, with the associated mechanisms yet to be fully understood. In our research, we examined the influence of SIRT6 on DOX-induced cardiomyocyte senescence using β-galactosidase and γ-H2AX staining. Additionally, we gauged the mRNA expression of senescence-associated genes, namely p16, p21, and p53, through Real-time PCR. Employing ELISA assay kits, MDA, and total SOD activity assay kits, we measured inflammatory factors TNF-α, IL-6, and IL-1β, alongside oxidative stress-related indicators. The results unequivocally indicated that SIRT6 overexpression robustly inhibited DOX-induced cardiomyocyte senescence. Furthermore, we established that SIRT6 overexpression suppressed the inflammatory response and oxidative stress induced by DOX in cardiomyocytes. Conversely, silencing SIRT6 exacerbated DOX-induced cardiomyocyte injury. Our investigations further unveiled that SIRT6 upregulated the expression of genes CD36, CPT1, LCAD, MCAD associated with fatty acid oxidation through its interaction with PPARα, thereby exerting anti-aging effects. In vivo , the overexpression of SIRT6 was observed to restore DOX-induced declines in EF and FS to normal levels in mice. Echocardiography and HE staining revealed the restoration of cardiomyocyte alignment, affording protection against DOX-induced myocardial senescence and injury. The findings from this study suggest that SIRT6 holds significant promise as a therapeutic target for mitigating DOX-induced cardiomyopathy.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
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.
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Drug Delivery and Translational Research
·
2024
·Vol. 14
·期 11
·3163-3172
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IF 5.7
Wang Lijie,Yu Dahai,Li Dan,Li Jing
The impact of optically active biomaterials on drug delivery remains a vital and hot topic. To reveal special advantages of optically active mesoporous silica nanoparticles in delivering drug in cells, optically active mesoporous silica nanoparticles deliver doxorubicin (DOX) with chiral behavior in cancer cells was studied. The present work focused on two types of optically active mesoporous silica nanoparticles named as levorotatory optically active mesoporous silica nanoparticles (LOA-MSNs) and dextrorotatory optically active mesoporous silica nanoparticles (DOA-MSNs) and examined their effects on cellular DOX delivery in cancer cells. The obtained LOA-MSNs and DOA-MSNs were regular spheres with particle diameters ranging from 200 to 250 nm, and their shell layer was filled with interlaced channels. Our results indicated that LOA-MSNs and DOA-MSNs did not exhibit cytotoxicity towards MCF-7 cells and B16 cells. The cytotoxicity of DOX-loaded LOA-MSNs and DOX-loaded DOA-MSNs were stronger than DOX owing to the synergistic retention and accumulation effect of nanoparticles. More importantly, DOX-loaded DOA-MSNs presented stronger cytotoxicity due to the higher synergistic retention and accumulation effect of DOA-MSNs. These findings suggest that DOA-MSNs with superior cellular delivery of DOX have great potential to advance the development of optical anti-tumor delivery system. Graphical abstract
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Biomedical Materials
·
2026
·Vol. 21
·期 3
·035017
·
IF 3.9
Lixia Fan,Xinren Xu,Huimin Luo,Yuke Xiang,Baixian Huang,Jun Wang,Ruixue Wang
Although chemotherapy remains a cornerstone of oncological treatment, its clinical application is severely hindered by the systemic toxicity and poor targeting efficiency inherent in conventional drug delivery systems. Given the relatively low levels of reactive oxygen species (ROS) in pathological tissues (<100 μM), there is an urgent need to develop stimuli-responsive carriers with superior sensitivity. In this study, we developed ditelluride-bridged carboxymethyl chitosan nanoparticles (DTeC NPs) as an innovative, ROS-triggered doxorubicin (DOX) release platform, using disulfide-crosslinked nanoparticles (DSC NPs) as a comparative control. Both nanocarriers exhibited a uniform particle size of approximately 200 nm and achieved high drug loading (∼25%) via electrostatic interactions with the polysaccharide backbone. Owing to the exceptional sensitivity of ditelluride bonds to oxidative environments, DTeC NPs demonstrated significantly accelerated degradation and drug release; notably, the cumulative DOX release reached 98.1% within 48 h in the presence of 100 μM H2O2. Furthermore, in vitro assays confirmed that DTeC/DOX NPs effectively enhanced cellular uptake. At a DOX concentration of 8 μg Ml−1, DTeC/DOX NPs reduced the viability of HepG2 and H22 cells to 27.4% and 33.9%, respectively, demonstrating significantly higher cytotoxicity compared to DSC/DOX NPs (35.9% for HepG2 and 45.8% for H22). In vivo studies further revealed that DTeC/DOX NPs achieved a tumor growth inhibition (TGI) rate of 72.29% in H22 tumor-bearing mice, markedly outperforming both free DOX (42.19%) and the disulfide-crosslinked control (60.81%). In summary, these findings underscore the immense potential of the ditelluride-crosslinking strategy for enhancing the precision and therapeutic efficacy of cancer chemotherapy.
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JOURNAL OF DRUG TARGETING
·
2026
·
IF 4.7
Ting-Ting Hu,Ying Ding,Yi-Ren Yao,Xin Zhang,Xi-Wen Zhang,Yang Gu
Doxorubicin (DOX), an anthracycline antibiotic, stands as one of the most potent and clinically ubiquitous chemotherapeutic agents for cancer treatment. Despite advances in clinical supportive care, strategies to prevent DOX-induced toxicity remain inadequate – with cardiotoxicity being a particularly devastating complication that can progress to heart failure. To address this unmet need, we engineered a novel core–shell biomimetic nanoparticle (NP) camouflaged with erythrocyte membranes, tailored for the targeted delivery of DOX to treat liver cancer while mitigating DOX-induced cardiotoxicity. This erythrocyte membrane-camouflaged biomimetic NP system exhibits an average diameter of 262.4 nm – an optimal size for prolonged systemic circulation – and possesses exceptional biocompatibility, coupled with enhanced responsiveness to the acidic tumour microenvironment. These synergistic features collectively augment the anti-tumour efficacy of DOX against hepatocellular carcinoma (HCC). Our findings highlight that the erythrocyte membrane-camouflaged NP serves as a promising biomimetic nanocarrier: it enables efficient delivery of chemotherapeutics to tumour sites while attenuating their off-target side effects (e.g. DOX-induced cardiotoxicity). This work thus provides a valuable strategy for improving the therapeutic index of anthracycline-based cancer treatments.
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MOLECULES
·
2026
·Vol. 31
·期 6
·
IF 5.1
Lizhen Yu,Dandan Wang,Zhongtao Hu,Xuefeng Hou,Shuxue Wang,Wenzhi Zhang,Lihua Li
Monitoring the concentration of doxorubicin (DOX) was critical for tumor treatment, but existing methods failed to cross cell membrane. Here, an electrochemical platform for intracellular DOX detection in MCF-7 cells based on membrane-permeation strategy was developed. A modified gold electrode was prepared via electrodepositing AuNPs and assembling SH-DNA. Concurrently, the silica nanosphere/gold nanocluster-circular transmembrane peptide (SiO2/AuNCs-iRGD) composite nanoparticles with membrane permeability, tumor targeting, and imaging capability were synthesized. After co-incubation of SiO2/AuNCs-iRGD with MCF-7 cells and DOX, followed by co-incubation with the DNA-modified electrode, intracellular DOX intercalated into the DNA backbone, and redox-generated electrons were transferred to the electrode to produce a concentration-correlated electrochemical signal. The modification of the electrode, the morphology of the composite nanoparticles and the detection process were characterized by means of SEM, TEM, CV, EIS, DPV, fluorescence spectroscopy and laser confocal imaging. Under the optimized conditions, the proposed method exhibited a wide detection range of 0.05–300 μmol/L, with a detection limit of 0.01 μmol/L. Moreover, the modified electrode demonstrated satisfactory regenerability, and the proposed method showed excellent reproducibility and stability. The development platform could offer a new strategy for real-time assessment of drug concentration within cultured breast cancer cells in vitro.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Jinsong Yin,Yuyun You,Juncong Mao,Jialong Qi,Xin Zhang,Yunfei Hong
Doxorubicin (DOX) is a widely used anthracycline whose dose-dependent cardiotoxicity limits its clinical efficacy. However, the mechanisms underlying its toxicity, particularly the regulatory network involving the Nod-like receptor protein 3 (NLRP3) inflammasome-gut-heart axis, remain incompletely understood. This study aimed to establish cellular and animal models of doxorubicin-induced cardiotoxicity (DIC) and investigate the role of the inflammasome in DIC-associated alterations in gut microbiota abundance. Rat cardiomyocytes (H9c2 cells) were treated with DOX 1, 10, 25, and 50 μmol/L concentrations to assess dose-dependent cardiotoxicity. In vivo, C57BL/6 J and NLRP3/MLKL/RIPK3 knockout (KO) mice received DOX (5 mg/kg, intravenous, every 2 days for 3 doses, cumulative 15 mg/kg) to establish a DIC model. We measured the physiological and biochemical parameters of mice peripheral blood using an automatic biochemical analyzer. Additionally, we quantified the mRNA expression levels of inflammatory factors using a reverse transcription polymerase chain reaction and observed cardiomyocyte apoptosis. Fecal samples were collected from each group for 16S recombinant DNA sequencing to analyze gut microbiota. DOX-induced H9c2 cell damage and inflammatory factor release activated the NLRP3 inflammasome and upregulated autophagy-associated proteins LC3I/II. NLRP3 KO attenuated DOX-induced cardiac damage, modulated the immune environment in mouse blood, and mitigated DIC. NLRP3 KO lowered the abundance of mucinophilic Akkermansia muciniphila and suppressed the cardiotoxic effects of DOX. The cardiotoxic effects of DOX were mediated via the NLRP3 inflammasome. NLRP3 inflammasome may mediate DIC by regulating the abundance of gut Akkermansia muciniphila .
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DRUG DELIVERY
·
2023
·
IF 6
Tianyu Zhang,Nuannuan Li,Ru Wang,Yiying Sun,Xiaoyan He,Xiaoyan Lu,Liuxiang Chu,Kaoxiang Sun
Doxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.
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JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Chen Xu,Shiyou Li,Jitang Chen,Huimin Wang,Zheng Li,Qingyuan Deng,Jiayuan Li,Xing Wang,Yuxuan Xiong,Zhijie Zhang,Xiangliang Yang,Zifu Li
Cancer stem cells (CSCs), enabled to self-renew, differentiate, and initiate the bulk tumor, are recognized as the culprit of treatment resistance, metastasis, and recurrence. Simultaneously eradicating CSCs and bulk cancer cells is crucial for successful cancer therapy. Herein, we reported that doxorubicin (Dox) and erastin co -loaded hydroxyethyl starch-polycaprolactone nanoparticles (DEPH NPs) eliminated CSCs and cancer cells by regulating redox status. We found that an excellently synergistic effect existed when Dox and erastin were co-delivered by DEPH NPs. Specifically, erastin could deplete intracellular glutathione (GSH), thereby inhibiting the efflux of intracellular Dox and boosting Dox-induced reactive oxygen species (ROS) to amplify redox imbalance and oxidative stress. The high ROS levels restrained CSCs self-renewal via downregulating Hedgehog pathways, promoted CSCs differentiation, and rendered differentiated cancer cells vulnerable to apoptosis . As such, DEPH NPs significantly eliminated not only cancer cells but more importantly CSCs, contributing to suppressed tumor growth, tumor-initiating capacity, and metastasis, in various tumor models of triple negative breast cancer . This study demonstrates that the combination of Dox and erastin is potent in elimination of both cancer cells and CSCs, and that DEPH NPs represent a promising treatment against CSCs-rich solid tumors .
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International Journal of Nanomedicine
·
2023
·
IF 8
Jingyi Zhou,Kangkang Li,Xinlong Zang,Yi Xie,Jinxiao Song,Xuehong Chen
Background Triple negative breast cancer (TNBC) is one of the most aggressive tumors with high metastasis and mortality, which constitutes 15~20% of all breast cancers. Chemotherapy remains main therapeutic option in the treatment of patients with TNBC.Methods We developed reactive oxygen species (ROS)-responsive galactosylated nanoparticles (DOX@NPs) as an efficiently targeted carrier for doxorubicin (DOX) delivery to inhibit the growth of TNBC in vitro and in vivo. DOX@NPs were composed of polyacrylate galactose and phenylboronic derivatives conjugation. The in vitro cytotoxicity, cellular uptake, cell apoptosis and cycle distribution of tumor cells treated with different formulations were investigated. Meanwhile in vivo biodistribution and antitumor effects were investigated in a 4T1 tumor-bearing mouse model.Results DOX@NPs showed good ROS responsiveness and rapid DOX release in the presence of H2O2. Furthermore, our data suggested that DOX@NPs could effectively trigger tumor cells apoptosis and cycle arrest, efficiently accumulate into tumor sites, and suppress tumor growth without adverse side effects.Conclusion Our results suggested DOX@NP with potent potential as a promising nanocarrier for TNBC therapy, which deserved further investigation for other cancer treatment.
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