JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Yicong Zhang,Yujia Wang,Hanming Zhang,Shiqi Huang,Yuai Li,Jiaying Long,Yikun Han,Qing Lin,Tao Gong,Xun Sun,Zhirong Zhang,Ling Zhang
Cholesterol is an indispensable component of most liposomes , heavily influencing their physical and surface properties. In this study, cholesterol in non-PEGylated liposomes was replaced by its analog, asiatic acid (AA), to generate liposomes with an alternative composition. These AA liposomes are generally smaller and more rigid than conventional liposomes, circulate longer in the body, and accumulate more in primary tumors and lung metastases in vivo . On the other hand, as an active ingredient, AA can decrease TGF-β secretion to inhibit the epithelial-mesenchymal transition (EMT) process, increase the sensitivity of tumor cells to doxorubicin (DOX), and synergize with DOX to enhance the immune response, thus improving their antitumor and anti-metastasis efficiency. Based on this rationale, DOX-loaded AA liposomes were fabricated and tested against triple-negative breast cancer (TNBC). Results showed that compared with conventional liposomes, the DOX-AALip provided approximately 28.4% higher tumor volume reduction with almost no metastatic nodules in the mouse model. Our data demonstrate that AA liposomes are safe, simple, and efficient, and thus in many situations may be used instead of conventional liposomes, having good potential for further clinical translational development.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 60
·期 10
·1595-1609
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IF 3.046
Junfeng Ding,Tianran Wang,Zhixiong Chen,Zhiqiang Lin,Xuesi Chen,Chaoliang He
The efficiency of antitumor immunotherapy is usually limited by the immunosuppressive tumor microenvironment (TME). In this study, we developed a chemo-immunotherapy strategy that is able to improve the immunosuppressive TME for enhancing the antitumor efficacy. The chemo-immunotherapy was achieved by the topical co-delivery of a chemotherapeutic drug, Doxorubicin (DOX), an immune checkpoint blocking antibody targeting programmed cell death protein 1 (aPD-1), and an indoleamine-2,3-dioxygenase (IDO) inhibitor, 1-methyl- d -tryptophan ( d -1MT) by using a thermosensitive polypeptide hydrogel. It was revealed that the sustained DOX release from the hydrogel caused the immunogenic cell death (ICD) of B16F10 cells in vitro, and the tumor cell lysates subsequently promoted the activation of dendritic cells (DCs). After intratumoral injection into B16F10 melanoma-bearing mice, the DOX/aPD-1/D-1MT co-loaded hydrogel exhibited enhanced tumor inhibition efficacy and prolonged animal survival time, compared to the DOX/aPD-1/D-1MT mixed solution, DOX-loaded hydrogel or DOX/aPD-1 co-loaded hydrogel. The improvement of immunosuppressive TME and enhancement of antitumor immune response after the local chemo-immunotherapy were demonstrated by the augmented activation of DCs and increased infiltration of CD8 + and CD4 + T cells, as well as enhanced secretion of pro-inflammatory cytokines. Therefore, the hydrogel-based local chemo-immunotherapy system holds great potential for effective antitumor treatment. Graphical
研究领域:
肿瘤学
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生物材料
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免疫学
✓ 已验证
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
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IF 19
Ruiyang Suo,Shuting Lu,Wang Qian,Shiqi Jin,Zhongkai Wang,Yi Li,Shuqi Li,Huan Ling,Yongchang Wei,Shiwen Huang,Haibo Xu,Bo Wu
Iodine-125 ( 125 I) brachytherapy, in combination with chemotherapy, is extensively utilized for tumor treatment. However, the primary challenge in concurrently implementing brachy-chemotherapy involves integrating the in situ implantation of 125 I seeds with the systematic administration of chemotherapeutic agents. Therefore, a novel 125 I seed modified with titanium dioxide nanotubes ( 125 I@TNT) is proposed to establish a localized drug release system. The titanium dioxide nanotubes are fabricated through anodic oxidation, exhibiting a uniform diameter of ≈100 nm and a thickness of 1 µm. These nanotubes effectively loaded doxorubicin (29.16 µg DOX/seed) while meeting the quality standards for subsequent applications, such as outer diameter and leak-proofness properties ( 125 I@TNT loaded with DOX is named 125 I@TNT-DOX). In vivo distribution studies revealed that 125 I@TNT-DOX delivered significantly more DOX concentrations to tumors compared to free DOX administered intravenously (5 mg kg −1 ) while delivering less DOX in the heart. Both in vitro and in vivo studies confirmed that apoptosis is the primary mechanism of cell death induced by 125 I@TNT-DOX. Additionally, 125 I@TNT-DOX effectively suppressed the growth of subcutaneous tumors in 4T1 and Hepa1-6 tumor-bearing mouse, surpassing other treatments, particularly the combination of 125 I seeds and intravenously administered DOX (5 mg kg −1 ). This system offers a promising strategy for enhancing concurrent brachy-chemotherapy.
研究领域:
肿瘤学
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纳米医学
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放射生物学
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DOI
高影响因子
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
·
2024
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IF 4
Luke Wei,Honglei Wang,Jiamin Wu,Jing Mao,Shijing Wang,Jieqiong Qiu
Doxorubicin (DOX), an anthracycline antibiotic used in cancer treatment, engenders health and environmental hazards owing to its adverse effects and subsequent discharge into wastewater, necessitating meticulous surveillance. Aptamer-based fluorescence biosensors (AFBs) have emerged as highly sensitive and cost-effective tools for this purpose. This study developed a label-free AFB by exploiting structural alterations in the DOX’s aptamer, induced by DOX and simulated by Thioflavin T (ThT). Binding affinities between DOX and its aptamer were scrutinized by molecular docking, circular dichroism, and UV–visible spectroscopy aimed at mimicking the interaction between aptamer and DOX and refining the DOX aptamer. One of the optimized aptamers (DOX-5) exhibited a detection limit of 3.15 nmol/L within a 5–100 nmol/L range. It proficiently detected DOX in milk and serum samples, with recovery rates of 98.1 %-102.6 % and 101.1 %-103.8 %, respectively. This methodology exemplifies a straightforward, economically viable, and productive strategy for DOX detection, significantly advancing antibiotic surveillance, food safety, and environmental vigilance measures.
研究领域:
生物化学
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环境科学
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医学检测
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DOI
高影响因子
ONCOLOGY RESEARCH
·
2025
·Vol. 33
·期 6
·1423
·
IF 4.1
JIANMIAO YANG,XIAOYAN SUN,TIANTIAN WANG,HAIQING ZHONG,MIN HAN,WUPING SHUAI,DONGHANG XU
Objectives Triphenylphosphine (TPP) and Doxorubicin (DOX) were conjugated to obtain Triphenylphosphine-Doxorubicin (TPP-DOX), which was applied in tumor cells for enhancement of DOX in mitochondria targeting. The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies. Methods TPP-DOX was synthesized using the carbodiimide method. In vitro experiments were conducted with 4T1 cells (mouse breast cancer cell line) to assess apoptosis induction, mitochondrial targeting, reactive oxygen species (ROS) production, and mitochondrial membrane potential. The research evaluates the effects of TPP-DOX, DOX, and their combinations with radiotherapy. A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy. Results TPP-DOX was successfully synthesized and scrupulously verified. In vitro experiments showed that compared to DOX, TPP-DOX exhibited enhanced tumor cytotoxicity, improved cellular uptake in 4T1 cells, and increased apoptosis induction. Combined with radiotherapy, TPP-DOX promoted mitochondrial ROS production, reduced mitochondrial membrane potential, and amplified its anti-tumor effect. In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity, promoted tumor tissue apoptosis, inhibited tumor angiogenesis, and showed a favorable in vivo safety profile. Conclusion The study confirmed that when combined with radiotherapy, TPP-DOX promoted tumor cell apoptosis, and effectively enhanced the anti-tumor effect. In sensitive cells, TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy. TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application. These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.
研究领域:
肿瘤学
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药理学
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放射生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Lulu An,Jimusi Wuri,Zhitong Zheng,Wenqui Li,Tao Yan
Chemotherapy has several adverse effects to patients, some of which are life-threatening. We hypothesized that Doxorubicin induced microbiome imbalance and intestinal damage may contribute to Doxorubicin induced cardiac dysfunction. Male adult (2–3 months) C57BL/6 mice were administered 3 mg/kg, 5 mg/kg, 7.5 mg/kg,15 mg/kg, 20 mg/kg doses of Doxorubicin. Echocardiography was performed at 7 and 14 days after Doxorubicin administration. 16S rRNA amplicon sequencing was used to characterize microbiome changes. Fecal microbiota transplantation (FMT) was performed to evaluate the role of the microbiota on Doxorubicin induced cardiac dysfunction. Doxorubicin dose dependently increases mortality rate and induces cardiac dysfunction. 5 mg/kg-Doxorubicin significantly induces decreased left ventricular ejection fraction (LVEF) and fraction shortening (FS) as well as increased cardiac fibrosis , inflammation and oxidative stress respond without increasing mortality. 5 mg/kg-Doxorubicin induces significant decreased colorectum length, increased loss of goblet cells, numbers of ulcers and infiltration of lymphocyte clusters and decreased tight junction protein ZO-1, as well as increased plasma endotoxin level measured by ELISA assay. 16S rRNA microbiota analysis shows that Doxorubicin-induced microbiota dysbiosis with decreased community richness compared with normal control mice. FMT to Doxorubicin-5 mg treated mice significantly improved cardiac function by increasing LVEF and FS as well as decreased perivascular and interstitial fibrosis ; increased colorectum length, decreased the loss of goblet cells,infiltration of lymphocyte clusters,the number of ulcers and plasma endotoxin level; improved microbiota composition, function and diversity with increased abundance of Alloprevotella, Prevotellaceae_UCG−001 and Rikenellaceae_RC9_gut_group. We find that normal fecal transplantation improves cardiac function, decreases gut damage and alter microbiota composition induced by Doxorubicin. The microbiota appears to contribute to heart-gut interaction.
研究领域:
药理学
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心脏病学
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微生物学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
Nano Research
·
2024
·
IF 9.5
Yu Yuanhao,Zuo Shiyi,Song Jiaxuan,Li Lingxiao,Liu Tian,Guo Jiayu,Li Yaqiao,Wang Danping,Lu Qi,Wang Helin,Zhou Dun,He Zhonggui,Liu Xiaohong,Sun Bingjun,Sun Jin
Albumin nanoparticles (ANPs) offer unique advantages for antitumor drug delivery system, including non-immunogenicity and inherent tumor-targeting capacity. At present, only a few products, such as ABRAXANE® and FYARRO™, have been approved for clinical applications. The poor affinity of doxorubicin (DOX) for albumin, coupled with its numerous severe adverse reactions, poses challenges in the fabrication of desirable albumin nanoparticles loaded with DOX. In this study, we developed prodrugs by conjugating fatty acids of varying lengths with DOX. Our aim was to investigate the balance between efficacy and safety through the selection of appropriate modules. We synthesized five pH-sensitive doxorubicin-fatty acid prodrugs. Compared to free DOX, all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 nm. Additionally, DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor cells. Significantly, the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids, impacting their in vivo pharmacokinetics, antitumor effectiveness and tumor accumulation. This research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs, and it builds a good platform for creating ANPs which prioritize high drug loading, high efficiency, and minimal side effects.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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产品关联
DOI
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2018
·Vol. 39
·期 10
·1681-1692
·
IF 3.562
Liu Hui-na,Guo Ning-ning,Guo Wang-wei,Huang-Fu Ming-yi,Vakili Mohammad Reza,Chen Jie-jian,Xu Wen-hong,Wei Qi-chun,Han Min,Lavasanifar Afsaneh,Gao Jian-qing
Breast cancer is the leading cause of cancer-related death for women, and multidrug resistance (MDR) is the major obstacle faced by chemotherapy for breast cancer. We have previously synthesized a doxorubicin (DOX) derivative by conjugating DOX with triphenylphosphonium (TPP) to achieve mitochondrial delivery, which induced higher cytotoxicity in drug-resistant breast cancer cells than DOX itself. Due to its amphiphilicity, TPP-DOX is difficult to physically entrap in nanocarriers. Thus, we linked it to hyaluronic acid (HA) by a novel ionic bond utilizing the specific bromide ion of TPP to form supra-molecular self-assembled structures (HA-ionic-TPP-DOX). The product was analyzed uisng 1 H-NMR, 13 C-NMR and mass spectrometry. The HA nanocarriers (HA-ionic-TPP-DOX) were shown to self-assemble into spherical nanoparticles, and sensitive to acidic pH in terms of morphology and drug release. Compared with free DOX, HA-ionic-TPP-DOX produced much greater intracellular DOX accumulation and mitochondrial localization, leading to increased ROS production, slightly decreased mitochondrial membrane potential, increased cytotoxicity in MCF-7/ADR cells and enhanced tumor targeting in vivo. In xenotransplant zebrafish model with the MCF-7/ADR cell line, both TPP-DOX and HA-ionic-TPP-DOX inhibited tumor cell proliferation without inducing significant side effects compared with free DOX. In addition, we observed a better anti-tumor effect of HA-ionic-TPP-DOX on MCF-7/ADR cells in zebrafish than that of TPP-DOX treatment. Furthermore, HA-ionic-DOX-TPP exhibited favorable biocompatibility and anti-tumor effects in MCF-7/ADR tumor-bearing nude mice in comparison with the effects of TPP-DOX and DOX, suggesting the potential of HA-ionic-TPP-DOX for the targeted delivery and controlled release of TPP-DOX, which can lead to the sensitization of resistant breast tumors.
研究领域:
肿瘤学
·
药学
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纳米技术
·
生物医学工程
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癌症研究
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceutics
·
2019
·Vol. 11
·期 2
·63
·
IF 4.773
Zar Chi Soe,Jun Bum Kwon,Raj Kumar Thapa,Wenquan Ou,Hanh Thuy Nguyen,Milan Gautam,Kyung Taek Oh,Han-Gon Choi,Sae Kwang Ku,Chul Soon Yong,Jong Oh Kim
In this study, a transferrin (Tf)-conjugated polymeric nanoparticle was developed for the targeted delivery of the chemotherapeutic agent doxorubicin (Dox) in order to overcome multi-drug resistance in cancer treatment. Our objective was to improve Dox delivery for producing significant antitumor efficacy in Dox-resistant (R) breast cancer cell lines with minimum toxicity to healthy cells. The results of our experiments revealed that Dox was successfully loaded inside a transferrin (Tf)-conjugated polymeric nanoparticle composed of poloxamer 407 (F127) and 123 (P123) (Dox/F127&P123-Tf), which produced nanosized particles (~90 nm) with a low polydispersity index (~0.23). The accelerated and controlled release profiles of Dox from the nanoparticles were characterized in acidic and physiological pH and Dox/F127&P123-Tfenhanced Dox cytotoxicity in OVCAR-3, MDA-MB-231, and MDA-MB-231(R) cell lines through induction of cellular apoptosis. Moreover, Dox/F127&P123-Tfinhibited cell migration and altered the cell cycle patterns of different cancer cells. In vivo study in MDA-MB-231(R) tumor-bearing mice demonstrated enhanced delivery of nanoparticles to the tumor site when coated in a targeting moiety. Therefore, Dox/F127&P123-Tfhas been tailored, using the principles of nanotherapeutics, to overcome drug-resistant chemotherapy.Keywords:doxorubicin;doxorubicin-resistant cancer;polymeric nanoparticles;transferrin
研究领域:
药学
·
纳米技术
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肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2015
·
IF 4.074
Yakun Ma,Xiaohui Fan,Lingbing Li
A doxorubicin conjugated prodrug incorporated acid-sensitive linkage between drug and Pluronic F127-chitosan (F127-CS) polymer was successfully synthesized. Subsequently a pH-sensitive polymeric micelle system was designed based on the conjugated prodrugs (F127-CS-DOX) to co-deliver doxorubicin and paclitaxel. Paclitaxel (PTX) was physically entrapped in the hydrophobic inner core of the micelles simultaneously. The structures of conjugates were analyzed by means of 1 H NMR and UV–vis spectrum. Size distribution and morphology of the micelles were observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results indicated that obtained micelles had good dispersity and the diameter was between 56.3 and 403.4 nm. The loading of PTX into the micelle increased with higher DOX content. DOX and PTX release from polymeric micelles followed an acid-triggered manner. Furthermore, in vivo pharmacokinetic study also showed that the area under the plasma concentration time curve (AUC 0–∞ ) values of PTX and DOX for PTX-loaded F127-CS-DOX micelles in rats were 3.97 and 4.38-fold higher than those for PTX plus DOX solution. These results suggested the PTX-loaded F127-CS-DOX micelles would be a promising carrier for co-delivering DOX and PTX.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 6
·期 4
·2602-2610
·
IF 3.84
Yanna Zhao,Jing Zhao,Chunying Hao,Meihua Han,Mincan Wang,Yifei Guo,Xiangtao Wang
An amphiphilic dendron–drug conjugate was synthesized via oligoethylene glycol (OEG) dendrons coupled with anticancer drug doxorubicin (DOX). The amphiphilic conjugate OEG–DOX (GD) self-assembled into spherical nanoparticles in aqueous solution, with mean diameters of approximately 212.5 nm. As an effective drug carrier, DOX was entrapped into GD to form drug-loaded nanoparticles (GD/D) with high drug loading content (24%, wt%), due to the enhanced hydrophobic/aromatic interactions between the DOX moiety in GD and free DOX. Besides, GD nanoparticles exhibited thermo-induced collapse and aggregation, therefore, the temperature-dependent drug release profiles of DOX from GD/D nanoparticles were measured and the possible mechanism was proposed. Moreover, hemolytic activity of GD/D revealed the good blood compatibility, and the cytotoxicity of DOX in GD/D was enhanced significantly in vitro against HepG2 cells. Overall, amphiphilic conjugate GD was considered to be potentially feasible to overcome formulation challenges for drug delivery and to be used in clinic.
研究领域:
药剂学
·
生物材料
·
肿瘤学
✓ 已验证
DOI
高影响因子
International Journal of Nanoscience
·
2023
·
IF 0.8
Yang Fu,Chaohui Ji,Zhiheng Ma,Defeng Xu,Hang Hu
In this work, we synthesized lactobionic acid-decorated diselenide-linked polyethylene glycol-doxorubicin conjugate (LA-PEG-SeSe-DOX) and prepared free DOX-loaded LA-PEG-SeSe-DOX(DOX@LA-PEG-SeSe-DOX) nanoparticles for hepatoma-targeted DOX delivery. LA-PEG-SeSe-DOX can self-assemble into nanoparticles in deionized water and DOX@LA-PEG-SeSe-DOX nanoparticles were prepared by loading free DOX into LA-PEG-Se-Se-DOX nanoparticles under sonication. DOX@LA-PEG-SeSe-DOX nanoparticles have high DOX loading content of 31.3%. The dynamic scattering analysis shows that DOX@LA-PEG-SeSe-DOX nanoparticles have small size (hydrodynamic diameter 4 5 . 6 9 ± 0 . 7 1 nm), near neutral zeta potential, and excellent colloidal stability. The in vitro drug release study indicates that DOX@LA-PEG-SeSe-DOX nanoparticles exhibit dual redox-responsive drug release characteristics. The cellular uptake study reveals that DOX@LA-PEG-SeSe-DOX nanoparticles can be taken up by hepatoma cells by asialoglycoprotein receptor (ASGPR)-mediated pathway. Finally, DOX@LA-PEG-SeSe-DOX nanoparticles exhibit enhanced cytotoxicity against HepG2 cells as compared to LA-PEG-SeSe-DOX nanoparticles, underlining the significance of releasing free DOX for effective tumor cell proliferation inhibition. This work provides a facile and effective strategy for targeted delivery of DOX to hepatoma cells.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）