Small
·
2025
·
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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Food Bioscience
·
2026
·
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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PHYSICAL CHEMISTRY CHEMICAL PHYSICS
·
2023
·Vol. 25
·期 17
·12458-12468
·
IF 3.3
Chufen Yang,Delin Wang,Wenyao Liu,Zexiong Yang,Teng He,Fang Chen,Wenjing Lin
Aiming at achieving the concurrent performances of high loading, well controlled release and active targeted delivery, folate (FA) modified dual pH/reduction-responsive mixed polymeric micelles were rationally assembled using FA-PEG-PDEAEMA and PEG-SS-PCL by dissipative particle dynamics (DPD) simulations. The optimized polymers PEG112-PDEAEMA40, FA-PEG112-PDEAEMA40, and PEG112-SS-PCL70 were synthesized and characterized using 1H NMR, FT-IR and GPC, and their mixed micelles were applied for doxorubicin (DOX) delivery. The drug loading capacity (LC) and encapsulation efficiency (EE) values of the MIX1 (FA-PEG112-PDEAEMA40/PEG112-SS-PCL70) at a DOX/polymer feeding ratio of 15 mg/30 mg were 20.22% and 50.69%, which were higher than those of single polymer micelles and MIX2 (PEG112-PDEAEMA40/PEG112-SS-PCL70). Particle size distributions, mesoscopic morphologies, DPD simulations and in vitro drug release profiles all confirmed the well-controlled release performance of the DOX-loaded micelles formed by MIX1: slow DOX release with a cumulative release of 20.46% in the neutral environment and accelerated release with a cumulative release of 74.20% at pH 5.0 + 10 mM DTT within 120 h, which were similar to those of MIX2. Cytotoxicity assay found that both MIX1 and MIX2 blank micelles were biocompatible, and a superior inhibitory effect of the FA-modified DOX-loaded micelles MIX1 on HepG2 cells was found compared to that of free DOX and non-FA-modified DOX-loaded micelles MIX2. All of these confirmed the superiority of MIX1 micelles with high loading capacity, well controlled release, and enhanced inhibitory effects on HepG2 cells, which might be a prospective candidate for anticancer drug delivery.
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2023
·
IF 3
Jing Wu,Yan Xu,Jiahong Yang,Xinyue Yu,Zhaodi Han,Linling Guo,Yin Huang,Yuxin Zhang
B vitamins play important roles in various physiological processes, including cell metabolism and DNA synthesis. The intestine is critical for the absorption and utilization of B vitamins, but few analytical methods for detecting intestinal B vitamins are currently available. In this study, we developed a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of 10 B vitamins in mouse colon tissue, including thiamin (B1), riboflavin (B2), nicotinic acid (B3), niacinamide (B3-AM), pantothenic acid (B5), pyridoxine (B6), pyridoxal 5′-phosphate (B6-5P), biotin (B7), folic acid (B9), and cyanocobalamin (B12). The method was thoroughly validated following the U.S. Food and Drug Administration (FDA) guidelines and yielded good results in terms of linearity (r 2 > 0.9928), lower limit of quantification (40–600 ng/g), accuracy (88.9–119.80 %) and precision (relative standard deviation ≤ 19.71 %), recovery (87.95–113.79 %), matrix effect (91.26–113.78 %), and stability (85.65–114.05 %). Furthermore, we applied our method to profile B vitamins in the colons of mice with breast cancer after doxorubicin chemotherapy treatment, which revealed that the doxorubicin treatment led to significant colon damage and accumulation of several B vitamins including B1, B2 and B5. We also confirmed the capability of this method for quantifying B vitamins in other intestinal tissues like the ileum, jejunum, and duodenum . The newly developed method is simple, specific, and useful for targeted profiling of B vitamins in mouse colon, with a potential for future studies on the role of these micronutrients in healthy and diseased states.
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BIOMATERIALS
·
2022
·
IF 15.304
Yongwei Hu,Yanteng Xu,Rachel L. Mintz,Xing Luo,Youqiang Fang,Yeh-Hsing Lao,Hon Fai Chan,Kai Li,Shixian Lv,Guojun Chen,Yu Tao,Yun Luo,Mingqiang Li
Tumor-positive resection margins after surgery can result in tumor recurrence and metastasis. Although adjuvant postoperative radiotherapy and chemotherapy have been adopted in clinical practice, they lack efficacy and result in unavoidable side effects. Herein, a self-intensified in-situ therapy approach using electrospun fibers loaded with a biomimetic nanozyme and doxorubicin (DOX) is developed. The fabricated PEG-coated zeolite imidazole framework-67 (PZIF67) is demonstrated as a versatile nanozyme triggering reactions in cancer cells based on endogenous H 2 O 2 and •O 2 − . The PZIF67-generated •OH induces reactive oxygen species (ROS) overload, implementing chemodynamic therapy (CDT). The O 2 produced by PZIF67 inhibits the expression of hypoxia-up-regulated proteins, thereby suppressing tumor progression. PZIF67 also catalyzes the degradation of glutathione , further disturbing the intracellular redox homeostasis and enhancing CDT. Furthermore, the introduced DOX not only kills cancer cells individually, but also replenishes the continuously consumed substrates for PZIF67-catalyzed reactions. The PZIF67-weakened drug resistance strengthens the cytotoxicity of DOX. The combined application of PZIF67 and DOX also suppresses metastasis-associated genes. Both in vitro and in vivo results demonstrate that the self-intensified synergy of PZIF67 and DOX on electrospun fibers efficiently prevents postsurgical tumor recurrence and metastasis, offering a feasible therapeutic regimen for operable malignant tumors.
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POLYMER INTERNATIONAL
·
2022
·Vol. 72
·期 2
·166-175
·
IF 3.213
Yi Liu,Lei Wang,Yifan Huang,Chao Hou,Binjie Xin,Tingxiao Li,Qian Jiang
Advanced application of coaxial electrospinning nanofibers in controlled drug release systems has gathered much attention since they have had a tunable structure for tailored release of drugs, including various proteins, growth factors, antibacterial and anticancer agents. The composite polymer poly( l -lactide- co -ε-caprolactone) (PLCL) blended with gelatin (GE) was used as the shell material to electrospin core–shell nanofibers. Model drug doxorubicin hydrochloride (DOX) was encapsulated in the core layers. The morphology and core–shell structure were evaluated by SEM and TEM respectively. The existence of DOX in the inner part of DOX/PLCL/GE nanofibers could be proved by Fourier transform infrared spectroscopy results. The water contact angle test results indicated that DOX/PLCL/GE nanofibers all possess good hydrophilicity with water contact angles as low as 51.2°. The in vitro release results indicated that the DOX/PLCL/GE nanofibers showed a sustained release profile for 480 h. The fitting results showed that the release kinetics of DOX from nanofibers was consistent with a Ritger–Peppas model, presenting a typical Fickian diffusion mechanism. Overall, the DOX/PLCL/GE core–shell nanofibers showed regulable mechanical properties and could be used as a promising drug release system for drug sustained release and tissue engineering. © 2022 Society of Chemical Industry.
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2022
·
IF 5.589
Tushuai Li,Zhihong Liu,Xiao Fu,Yongquan Chen,Shenglong Zhu,Jie Zhang
Chemo-immunotherapy has gained increasing attention as one of the most promising combination therapy strategies to battle cancer. In this study, the therapeutic nanoparticles (TNPs) co-delivering doxorubicin (DOX) and IL-12 (IL-12) were developed for chemo-immunotherapy combination therapy on liver cancer. TNPs were synthesized based on the ionic interactions between cationic chitosan (Ch) and anionic poly-(glutamic acid) (PGA). DOX and IL-12 loaded in TNPs presented prolonged circulation in blood, efficient accumulation in tumors, and internalization in tumor cells. After that, DOX and IL-12 were co-released in the tumor microenvironment . The locally responsive property of TNPs could subsequently re-educate macrophages. More significantly, TNPs with no obvious side effects can remarkably inhibit the H22 tumor growth in vivo. A low dosage of loaded IL-12 in TNPs can effectively polarize macrophages toward the M1 phenotype to reduce tumor burden, further enhancing the antitumor efficacy. Our results suggest that the self-stabilized TNPs could be a secure and effective drug carrier for intravenous administration when deprived of protective agents.
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
·
2022
·
IF 6.814
Chunhong Mo,Zhao Wang,Jianying Yang,Yiqiang Ouyang,Qian Mo,Shuting Li,Ping He,Limin Chen,Xinchun Li
Herein, we present the facile design and construction of a nanodrug system integrating targeted drug delivery and synergistic chemo-photothermal antitumor activity . MoS 2 nanosheets were synthesized and modified by α ν β 3 integrin binding peptide (Arg-Gly-Asp, RGD) using lipoic acid functionalized polyethylene glycol (LA-PEG-COOH), forming a well dispersed and targeted delivery nanocarrier . Further, covalent coupling of antitumor drug , thiolated doxorubicin (DOX) via disulfide linkage resulted in a novel nanodrug, RGD/MoS 2 /DOX. The prepared nanocarrier showed favorable stability, biocompatibility and photothermal conversion efficiency. Fluorescence imaging revealed that Hela cells could endocytose far more nanodrug than H9c2 normal myocardial cells due to the targeted delivery characteristic. Particularly, GSH-induced disulfide bond cleavage facilitated the effective release of DOX from the nanodrug in the tumor microenvironment . The survival rate of Hela cells incubated with the nanodrug for 48 h was 22.2 ± 1.2%, which dramatically reduced to 8.9 ± 1.4% in combination with 808 nm NIR irradiation, demonstrating powerful photothermal induced tumor-killing efficacy. In contrast, the survival rates of H9c2 cells treated by the nanodrug and free DOX were 68.5 ± 2.6% and 6.7 ± 2.6%, respectively, an indication of the notably alleviated cardiotoxicity of the designed nanodrug. The cell apoptosis experiment further verified the synergistic chemo-photothermal effect, thus paving a way toward design of high-efficiency and low-toxicity antitumor nanodrug.
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OPTICAL MATERIALS
·
2022
·
IF 3.754
Wenkun Zhang,Rong Ma,Shuo Gu,Liting Zhang,Ningbo Li,Jie Qiao
Nitrogen and phosphorus co-doped carbon dots (NPCDs) with bright blue fluorescence were established by a hydrothermal method using alanine and diammonium phosphate as raw materials. The NPCDs were characterized by transmitted electron microscopy , X-ray photoelectron spectroscopy, Fourier transform infrared spectrometry , ultraviolet–visible absorption (UV–vis), and fluorescence spectroscopy to investigate the morphology, elemental composition, and optical properties . The NPCDs had good water solubility, high dispersibility with an average diameter of only 2.77 nm, and satisfactory optical properties with a fluorescence quantum yield of 17.2%. The NPCDs were employed for the detection of doxorubicin (DOX). A good linear response of the NPCDs in the range 0.5–6.5 μM was obtained for DOX with a detection limit of 12 nM. The NPCDs were also applied to the analysis of real samples, urine and serum, with a recovery of 92.0–109.3%. The low cytotoxicity and good biocompatibility of the NPCDs were indicated by an MTT assay and cell imaging of HeLa cells. Compared with other detection systems, using NPCDs for DOX detection was a facile and efficient method with good selectivity and sensitivity.
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Drug Delivery and Translational Research
·
2022
·Vol. 12
·期 10
·2537-2549
·
IF 5.671
Wang Yingli,Chen Lixue,Zhang Zonglin,Liu Wenqi,Li Lei
Liposomal delivery system that concurrent delivery of multiple drugs can improve efficacy of cancer treatments, yet remain challenging because of differential properties, fairly low loading thresholds of many drugs, and drug burst release. Here, we report a ratiometrically designed liposomal nanoplatform with synergistic efficacy, utilizing remote loading to co-encapsulate ROS-sensitive paclitaxel prodrug (PSN) and doxorubicin (DOX). This novel dual-delivery liposomes possess high two-drug encapsulation efficacy and colloidal stability, resulting in synergistic cytotoxicity, extended blood circulation, favorable biodistribution, always maintain the ratiometrically synergistic drug ratio in vivo, and potent synergistic anticancer activity. Such a combination of PSN and DOX with synergistic effects encapsulated in a safe and effective dual-delivery liposomal nanomedicine may hold promise for the further clinical translation and provides a new strategy for high-efficient combination chemotherapy.
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Frontiers in Pharmacology
·
2023
·
IF 5.6
Hui Zhang,Qingwen Xue,Zihan Zhou,Ningning He,Shangyong Li,Cheng Zhao
Breast cancer (BC) is the most common malignancy in women worldwide, and the standard treatment is chemotherapy or radiotherapy after surgery. In order to reduce the side effects of chemotherapy, various nanoparticles (NPs) have been discovered and synthesized, which has become a promising treatment for BC. In this study, a co-delivery nanodelivery drug system (Co-NDDS) was designed and synthesized with 2,3-dimercaptosuccinic acid (DMSA) coated Fe 3 O 4 NPs as core encapsulated into chitosan/alginate nanoparticles (CANPs) shell, doxorubicin (DOX) and hydroxychloroquine (HCQ) as loading drugs. Smaller NPs carrying DOX (FeAC-DOX NPs) were loaded into larger NPs containing HCQ (FeAC-DOX@PC-HCQ NPs) by ionic gelation and emulsifying solvent volatilization methods. The physicochemical properties of this Co-NDDS were characterised, followed by in vitro studies of the anticancer effects and mechanisms using two different BC cell lines, MCF-7 cells and MDA-MB-231 cells. The results indicated that the Co-NDDS showcases exemplary physicochemical qualities and encapsulation capacity, facilitating accurate intracellular release through pH-sensitive attributes. Importantly, NPs can significantly increase the in vitro cytotoxicity of co-administered drugs and effectively inhibit the autophagy level of tumour cells. The Co-NDDS constructed in this study provides a promising strategy for the treatment of BC.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yaoxun Zeng,Jiongpeng Yuan,Zhili Ran,Xiaoguang Zhan,Xinyi Li,Huiling Ye,Jiapeng Dong,Guining Cao,Zhenxing Pan,Ying Bao,Junze Tang,Xujie Liu,Yan He
Surgical resection remains the primary treatment modality for bone tumors. However, it is prone to local bone defects and tumor recurrence. Therefore, there is an urgent need for multifunctional biomaterials that combine tumor treatment and bone repair after bone tumor surgery. Herein, a chitosan composite scaffold (CS/DOX@Ti-MOF) was designed for both tumor therapy and bone repair. Among them, the amino-functionalized Ti-based metal-organic framework (NH 2 -MIL-125 (Ti), Ti-MOF) has a high specific surface area of 1116 m 2 /g and excellent biocompatibility, and promotes osteogenic differentiation. The doxorubicin (DOX) loading capacity of Ti-MOF was 322 ± 21 mg/g, and DOX@Ti-MOF has perfect antitumor activity. Furthermore, the incorporation of DOX@Ti-MOF improved the physical and mechanical properties of the composite scaffolds, making the scaffold surface rough and favorable for cells to attach. CS/DOX@Ti-MOF retains the unique properties of each component. It responds to the release of DOX in the tumor microenvironment to remove residual tumor cells, followed by providing a site for cell attachment, proliferation, and differentiation. This promotes bone repair and achieves the sequential treatment of postoperative bone tumors. Overall, CS/DOX@Ti-MOF may be a promising substitute for postoperative bone tumor clearance and bone defect repair. It also provides a possible strategy for postoperative bone tumor treatment.
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