JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2022
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IF 9.965
Xiulan Weng,Wei Chen,Wanling Cai,Gary Owens,Zuliang Chen
Due to its low-cost, eco-friendliness and easy mode of separation biosynthesized magnetic ferroferric oxide (Fe 3 O 4 ) can be successfully used for the removal of organic contaminants from wastewater. However, there are some challenges that to date have limited this compound’s practical removal efficiency. Thus, in this study, a cobalt-based zeolitic imidazole frameworks (ZIF-67) coated biosynthesized ferroferric oxide@silicon dioxide (Fe 3 O 4 @SiO 2 ) magnetic composite (Fe 3 O 4 @SiO 2 /ZIF-67) was prepared to address these issues and subsequently used to remove doxorubicin hydrochloride (DOX). Characterization results showed that the fabricated composite exhibited significant magnetic properties (16.1 emu·g −1 ) with a size ranging between 50 and 250 nm. The amount of DOX adsorbed by the composite (90.7 mg·g −1 ) was much higher than either of the component parts, which were only 35.7 and 82.5 mg·g −1 for Fe 3 O 4 @SiO 2 and ZIF-67 respectively. This indicated enhanced DOX adsorption by Fe 3 O 4 @SiO 2 /ZIF-67. The DOX adsorption best fit a pseudo-second order kinetic and Langmuir adsorption model. These studies suggested that the DOX adsorption mechanism involved a combination of electrostatic interactions , π-π stacking, hydrogen bonding and pore filling. Regeneration and application studies, exposing Fe 3 O 4 @SiO 2 /ZIF-67 to real water samples, practically demonstrated that Fe 3 O 4 @SiO 2 /ZIF-67 with propensity for magnetic separation and recycle is a promising nanomaterial for DOX removal.
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ARABIAN JOURNAL FOR SCIENCE AND ENGINEERING
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2025
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IF 2.9
Li Caixia,Zhou Qin,Chao Zhenzhen,Li Liang
In this study, the preparation of pH- and reduction-responsive doxorubicin (DOX)-loaded hyaluronate acid-F127 supramolecular hydrogels (DOX@Gels) with targeting ability due to the incorporation of hyaluronic acid is described. By combining Pluronic F127-modified hyaluronic acid (HA-F127), disulfide-modified β-cyclodextrin, α-cyclodextrin, and DOX, hydrogels were constructed through host–guest complexation and hydrogen bonding interactions, and a tailored platform for targeted drug delivery was provided. The chemical composition and rheological properties were comprehensively analyzed. Considering the controlled complexation between DOX and the hydrogel skeleton and the ability of HA to target cancer cells, controlled drug release from the hydrogel G[15,5,5] was investigated under various conditions in vitro. The cumulative amount of DOX released from hydrogel G[15,5,5] showed superior pH- and reduction-controlled release behavior. These results were likely caused by the HA-F127 ester bonds cleavage in acidic environments and the S‒S bond cleavage within the hydrogel networks in the presence of glutathione. Furthermore, the DOX release kinetics were analyzed using Higuchi and Korsmeyer-Peppas models. The results demonstrated that the experimental data was effectively fit with these two models, and the data fitted by using Korsmeyer-Peppas also indicated nonFickian diffusion kinetics of the DOX being released from hydrogels. Owing to the ability of HA to target SKOV-3 cells, the cytotoxicity experiments revealed that DOX@G[15,5,5] exhibited more significant anticancer effects than free DOX. Consequently, DOX@Gels containing HA have emerged as promising candidates for the targeted delivery and release of anticancer drugs.
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BIOMATERIALS
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2014
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IF 8.312
Shixian Lv,Zhaohui Tang,Mingqiang Li,Jian Lin,Wantong Song,Huaiyu Liu,Yubin Huang,Yuanyuan Zhang,Xuesi Chen
Despite progress, combination therapy of different functional drugs to increase the efficiency of anticancer treatment still remains challenges. An amphiphilic methoxy poly(ethylene glycol)- b -poly( l -glutamic acid)- b -poly( l -lysine) triblock copolymer decorated with deoxycholate (mPEsG- b -PLG- b -PLL/DOCA) was synthesized and developed as a nanovehicle for the co-delivery of anticancer drugs: doxorubicin (DOX) and paclitaxel (PTX). The amphiphilic copolymer spontaneously self-assembled into micellar-type nanoparticles in aqueous solutions and the blank nanoparticles possessed excellent stability. Three different domains of the copolymer performed distinct functions: PEG outer corona provided prolonged circulation, middle biodegradable and hydrophilic PLG shell was designed for DOX loading through electrostatic interactions , and hydrophobic deoxycholate modified PLL served as the container for PTX. In vitro cytotoxicity assays against A549 human lung adenocarcinoma cell line demonstrated that the DOX + PTX co-delivered nanoparticles (Co-NPs) exhibited synergistic effect in inducing cancer cell apoptosis. Ex vivo DOX fluorescence imaging revealed that Co-NPs had highly efficient targeting and accumulation at the implanted site of A549 xenograft tumor in vivo . Co-NPs exhibited significantly higher antitumor efficiency in reducing tumor size compared to free drug combination or single drug-loaded nanoparticles, while no obvious side effects were observed during the treatment, indicating this co-delivery system with different functional antitumor drugs provides the clinical potential in cancer therapy.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2020
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IF 4.845
Yunbo Nie,Dan Li,Ying Peng,Shengfeng Wang,Shuo Hu,Miao Liu,Jinsong Ding,Wenhu Zhou
The RNA-cleaving DNAzyme (DZ) holds promising potential for RNA interference (RNAi) applications and is favored over siRNA owing to its high chemical stability, biocompatibility , predictable activity, and substrate versatility. However, its pharmaceutical applications for disease treatment are limited by the requirement of metal cofactor for activation, as well as the lack of effective co-delivery systems to combine with other therapeutic modalities. Herein, we designed and constructed metal organic framework (MOF) coated MnO 2 nanosheets to realize the co-delivery of a survivin inhibiting DZ and doxorubicin (DOX) for chemo-gene combinatorial treatment of cancer. In our design, the DOX was adsorbed on MnO 2 planar surface, and the DZ was loaded into the MOF shell layer through the coordination between Mn 2+ and tannic acid . The nano-system could stably encapsulate the payloads under physiological condition, but rapidly degraded after endocytose into tumor cells in response to intracellular stimuli, resulting in triggered drugs release. Notably, the coreleased Mn 2+ could act as metal cofactor for effective DZ activation. Both in vitro and in vivo studies have demonstrated the enhanced anti-tumor efficacy of the nanosystem, with co-contributions from anti-neoplastic DOX, survivin silencing effect of DZ, and to some extent, ROS generation by Mn 2+ . This work provides an ingenious strategy to address the key limitation of DZ for RNAi applications and realize the combination of DZ with other therapeutic modalities, in which the DZ can be in-situ activated for target gene silencing.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2011
·Vol. 401
·期 7
·2143-2152
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IF 3.841
Deng Bin,Wang Zhiming,Song Jian,Xiao Yuxiu,Chen Dan,Huang Jun
The doxorubicin (DOX) uptake in single human leukemia K562 cells with changes in both drug dosage and exposure period was studied using capillary electrophoresis (CE) coupled with laser-induced fluorescence (LIF) detection. The cells were treated with DOX at different concentrations (1, 3, 10, 20, 30, and 50 μM) and for different exposure times (1, 3, 5, 24, and 48 h). At least 20 cells were analyzed for each DOX-treated cell population. A marked heterogeneity in DOX uptake among single cells was observed, because the relative standard deviation of the uptake of DOX by single cells ranged from 24.0% to 61.1% within each cell population. The cell-to-cell heterogeneity in DOX uptake first decreased and then became constant with increasing drug concentration, but it did not exhibit regular variation with increasing exposure time. The mean DOX uptake was a linear function of drug concentration ( r ≥ 0.9667). In terms of the correlation with exposure time, the mean DOX uptake reached its maximum at 3 h for the cell populations treated with 1–10 μM DOX, while it kept increasing during 48 h exposure of cell populations to 20–50 μM DOX. Because it eliminates DOX fluorescence quenching and sample loss, the CE-LIF method directly detects the true DOX uptake by single cells, and thus presents accurate information on both the cell-to-cell heterogeneity in DOX uptake and the patterns of DOX uptake in K562 cells as functions of drug concentration and exposure time.
CE-LIF analysis of DOX uptake in single human leukemia K562 cells. a DOX uptakes of single K562 cells treated with 1 μM DOX for 3 h; The RSD% for the DOX uptake of single K562 cells as functions of b the extracellular DOX concentration and c the exposure time; Mean DOX uptake of single K562 cells as functions of d the extracellular DOX concentration and e the exposure time
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MICROCHEMICAL JOURNAL
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2025
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IF 5.1
Raj Kumar Parajuli,Jin Liu,Shree Krishna Tamang,Govinda Gurung,Kumar Neupane,Yao Wang,Christopher D. Snow,Matt J. Kipper,Laurence A. Belfiore,Jianguo Tang
Patient urine may provide relatively convenient access to biomarkers, but it is challenging to directly and visibly sense drugs via fluorescence quenching or enhancement. This study reports the synthesis of water-soluble and fluorescence-stable terbium-induced nanoaggregates (TIPAs) of polystyrene-poly(acrylic acid) (PS- b -PAA), containing a novel [Tb( acac )Cl 2 ( phen )Cyclen] complex, to sense doxorubicin ( dox ) in urine. The TIPAs demonstrated remarkable water stability, maintaining high fluorescence intensity in aqueous environments, with a fluorescence lifetime of 55.5 ms and a quantum yield (QY) of 4.60 %, making them ideal for smart sensing applications. The novel aggregate exhibits an orthorhombic structure, with its photophysical properties elucidated through simulated modeling. Fluorescence quenching studies indicate dynamic interactions between TIPAs and dox in urine, achieving a limit of detection (LOD) of 13.77 μM, highlighting the method's sensitivity for real-time dox monitoring. The emission of TIPAs in the visible range (450–600 nm) overlaps with the absorption spectrum of dox , enabling efficient energy transfer and fluorescence quenching. These findings highlight the potential of TIPAs as stable, fluorescence-based sensors for drug monitoring, with promising applications in bioimaging and diagnostics within cancer therapy.
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Small
·
2025
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IF 12.1
Zhi-Nan Wang,Xi Liu,Xiaowei Zhu,Shidong Hu,Kun Zhang,Xiao-Ting Li,Bin′en Nie,Ying-Shi Sun
Doxorubicin (DOX), a widely used anthracycline chemotherapeutic, is clinically limited by cumulative and dose-dependent cardiotoxicity. Oxidative stress and inflammation are central pathogenic mechanisms of DOX-induced cardiomyopathy (DIC), characterized by extensive innate immune cells infiltration into the injured myocardium. The immune landscape of DIC mouse models is systematically characterized, identifying macrophages as the predominant immune subset. Based on this, a hybrid nanozyme (PB@CeO 2 NPs) is developed, comprising Prussian blue nanoparticles (PB NPs) and cerium oxide nanoparticles (CeO 2 NPs). The PB NPs core provides magnetic resonance imaging (MRI) contrast, while CeO 2 NPs surface modification enhances immune cell uptake, promotes retention in inflamed cardiac tissue, and augments reactive oxygen species (ROS) scavenging and anti-inflammatory efficacy. In vitro experiments demonstrate that PB@CeO 2 NPs alleviate mitochondrial damage, inhibit apoptosis, and induce macrophage M2 polarization. In vivo studies show that PB@CeO 2 NPs facilitate myocardial accumulation, reduce cardiac inflammation and fibrosis, and improve cardiac function. By integrating the antioxidative and anti-inflammatory effects of PB@CeO 2 NPs with inflammation-mediated immune cell retention in injured myocardium, this study presents a promising nanotherapeutic platform for targeted and precise intervention in anthracycline-induced cardiotoxicity.
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MICROCHEMICAL JOURNAL
·
2025
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IF 5.1
Qian Bi,Hongmei Zhang,Han He,Qian Li,Baoting Dou
Doxorubicin (DOX) is a frequently prescribed chemotherapy medication for a range of cancers. It is essential to monitor the levels of doxorubicin in human biological fluids to ensure effective treatment. An efficient electrochemical sensor for amplified detection of DOX is developed in this work. The strand displacement reaction is initiated when the blocking probe, which attaches to the terminal toehold sequence of the immobilization probe, is released due to the selective recognition of DOX with the aptamer probe. The secondary toehold region is then available for hybridization with the methylene blue (MB)-labeled signal probe, causing the blocking probe to be displaced and activating the molecular machine. Consequently, the blocking probe is reused in a cyclical manner, with numerous signal probes being attached to the sensor surface, resulting in a significant increase in current for quantitative analysis. This technique successfully detected DOX in human serum samples with high selectivity and sensitivity, reaching a detection limit of 670 fM. The proposed research offers a novel approach to identifying various biomarkers, with the potential to significantly advance clinical diagnosis and drug research.
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International Journal of Nanomedicine
·
2026
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IF 8.7
Ling Li,Wenjing Xie,Haixia Sun,Houqiang Yu,Cai Wang,Min Zheng,Peng Shi,Hongan Tian,Tongqiang Xiong
Background Tumor recurrence and metastasis are important factors affecting the efficacy of transhepatic arterial chemoembolization. To prolong the survival of patients, comprehensive interventional therapy and antitumor drugs that can control their release need to be developed.Methods Poly(N-isopropylacrylamide-co-acrylic acid) nanogels are firstly self-assembled with doxorubicin, the constructed doxorubicin-loaded nanogels were then emulsified with iodized oil under high-shear conditions to form doxorubicin–iodized oil nanogel suspensions (Dox-TIPE). The structural characteristics, thermosensitive properties and rheological properties were evaluated. The in vitro biocompatibility and drug release behavior of Dox-TIPE were assayed and in vivo interventional therapy was examined in a VX2 rabbit liver cancer model.Results Dox-TIPE can effectively exert the dual advantages of chemoembolization therapy, achieving a superior therapeutic effect on inhibiting rabbit liver tumor growth. It promotes TUNEL expression in the tumor boundary region while reducing Ki67 expression, which results in decreased tumor cell proliferation and increased apoptosis rates. Furthermore, Dox-TIPE effectively suppresses the expressions of HIF-1α, VEGF, and CD31 in tumor target areas, thereby preventing the formation of tumor neovascularization and collateral circulation.Conclusion We successfully produced Dox-TIPE which offers a multifunctional platform combining embolization, chemotherapy, imaging, and immunomodulation. This novel embolic material shows strong potential to address current limitations of TACE in liver cancer treatment and may serve as a promising candidate for next-generation embolization therapies.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
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IF 6
Yue Wei,Yangyi Chen,Huajing Zhang,Qiao Li,Huajuan He,Xiao Liang,Shiyuan Lin,Hui Chen,Wei Wu,Wei Zhang
A kind of purine nucleoside-chitosan-silybin (PN-CS-SB) polymeric micelles were developed for enhancing the oral absorption of doxorubicin (DOX) by intestinal nucleoside transporter mediation, the inhibition of P-glycoprotein (P-gp) efflux and CYP3A4 metabolism. The four types of PN, including adenosine, deoxyadenosine, guanosine and deoxyguanosine, respectively, and silybin, were conjugated to chitosan via the linker succinic acid. The synthesized PN-CS-SB were identified by 1 H NMR and FT-IR, and the doxorubicin (DOX)-loaded micelles were prepared by ultrasonication. The micelles demonstrated a series of the excellent properties, including the high drug loading capacity of above 8.2%, the regular spherical shapes with the small particle sizes of below 150 nm, and the low critical micelle concentration of below 5.82 × 10⁻⁶ g/mL. The oral bioavailability of the DOX-loaded micelles against DOX solution achieved to as high as 453.28%. The rapid and tremendous absorption of micelles was visually demonstrated by in vivo imaging. The micelle absorption mechanism was proved to be nucleoside transporter-mediation as well as the dual inhibition of P-gp and CYP3A4 by the cellular uptake, enzyme inhibition and immunofluorescence location test. The cellular endocytosis and transportation pathway of micelles across intestinal epithelial cells involved nucleoside transporter target, caveolin mediation or macropinocytosis with energy consumption. Download: Download high-res image (234KB) Download: Download full-size image
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Food Bioscience
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2026
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IF 6.2
Qidong Xue,Kangning Li,Jie Mi,Dekun Cheng,Ruijie Liu,Ming Chang
Doxorubicin (Dox)-induced cardiotoxicity is a major dose-limiting adverse effect of chemotherapy and is closely linked to oxidative stress and impaired endogenous antioxidant defenses. Food-derived polyphenols that reinforce cellular redox resilience may therefore offer a safe adjuvant strategy. Pinus koraiensis nut skin (PNS), an underutilized nut-processing residue, is rich in polyphenols, yet its bioactive profile and cardioprotective mechanism remain insufficiently defined. Here, we optimized the extraction of PNS polyphenols (PNSP), profiled its phytochemical composition, and investigated its protective effects against Dox-induced cardiomyopathy (DIC). Under optimized conditions, PNSP exhibited strong in vitro antioxidant capacity. UPLC-Q-TOF-MS tentatively identified 26 phytochemicals dominated by procyanidins and flavonoids. In a zebrafish DIC model, post-treatment with PNSP (10 – 40 μg/mL) dose-dependently rescued cardiac dysfunction. Notably, 40 μg/mL PNSP restored heart rate from 112.00 ± 24.28 to 157.00 ± 13.98 beats/min and reduced ROS accumulation. Mechanistically, PNSP reactivated endogenous antioxidant enzymes (SOD, GSH-Px) by activating the Nrf2/Keap1 signaling pathway. Procyanidin C1 and the Pinus -specific flavonoid pinobanksin 3-acetate were identified as key ligands that competitively occupy the Keap1 Kelch pocket, thereby facilitating Nrf2 nuclear translocation. This non-covalent, competitive activation mechanism was robustly validated by molecular docking, stable Keap1 protein expression, and enhanced ARE-luciferase reporter activity. Collectively, these findings identify PNSP as a food-relevant Nrf2 activator with potential to mitigate chemotherapy-associated cardiotoxicity, highlighting its potential as a high-value functional food ingredient.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Ning Jiang,Fengying Yin,Qianqian Dang,Guoliang Chen,Xiaoxia Wu,Saining Wang,Xuelin Wang,Lin Sun
MOF-ABZ significantly improved apparent aqueous dispersibility of ABZ. • MOF-ABZ induced ROS-associated ICD signaling in HCC cells. • MOF-ABZ potentiated the antitumor efficacy of low-dose DOX while reducing systemic toxicity in vivo . Doxorubicin (DOX) is widely used to treat hepatocellular carcinoma, but its dose-dependent cardiotoxicity limits its clinical application. Although dose reduction can mitigate cardiac injury, it often weakens antitumor efficacy, underscoring the need for effective sensitization strategies. Albendazole (ABZ) can induce reactive oxygen species (ROS) production, which may promote immunogenic cell death (ICD); however, its poor aqueous solubility restricts therapeutic application. To overcome this limitation, γ-cyclodextrin-based metal-organic frameworks were used to encapsulate ABZ, generating MOF-ABZ for low-dose DOX sensitization. MOF-ABZ improved ABZ dispersion and induced ROS-associated immunogenic responses in HepG2 cells, as indicated by the release of damage-associated molecular patterns (DAMPs), dendritic cell maturation, and early CD8 + T-cell activation; these effects were attenuated by N -acetylcysteine. MOF-ABZ further sensitized HepG2 cells to DOX, reducing the DOX IC₅₀ from 119.5 to 91.3 ng/mL. In H22 tumor-bearing mice, the combination of low-dose DOX and MOF-ABZ achieved tumor inhibition comparable to that of high-dose DOX alone and superior to that of low-dose DOX monotherapy, with less body-weight loss, milder histological myocardial damage, and cytokine changes consistent with immunomodulatory activity. In conclusion, through efficient ABZ delivery, MOF-ABZ enhances the antitumor efficacy of low-dose DOX, and these ROS-associated immunogenic responses potentially contribute to this sensitization effect, providing a promising strategy to improve the therapeutic index of DOX in HCC models. Download: Download high-res image (174KB) Download: Download full-size image
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