查找使用阿拉丁产品的科研文献

Hyaluronic acid-modified yeast β-glucan particles delivering doxorubicin for treatment of breast cancer

Fangzhou He,Conghua Xie,Xiaojuan Xu

Breast cancer is one of the most threatening cancers that poses a great risk to women's health . The anti-tumor drug doxorubicin (DOX) is one of commonly used drugs in the treatment of breast cancer. However, the cytotoxicity of DOX has always been an urgent challenge to be solved. In this study, we report an alternative drug delivery system delivering DOX for reducing its physiological toxicity by using the yeast β-glucan particle (YGP) with a hollow and porous vesicle structure. Briefly, amino groups were grafted onto the surface of YGP with the silane coupling agent, then the oxidized hyaluronic acid (OHA) was attached by Schiff base reaction to get HA-modified YGP ( [email protected] =C-HA), finally DOX was encapsulated into [email protected] =C-HA to get DOX-loaded [email protected] =C-HA ( [email protected] =C-HA/DOX). In vitro release experiments exhibited the pH-responsive DOX release from [email protected] =C-HA/DOX. Cell experiments displayed that [email protected] =C-HA/DOX had good killing effect on both MCF-7 and 4T1 cells and could be internalized into these cells through CD44 receptors, showing targetability to cancer cells. Furthermore, [email protected] =C-HA/DOX could effectively inhibit tumor growth and reduce the physiological toxicity of DOX. Thus, the YGP-based vesicle provides an alternative strategy for lowering the physiological toxicity of DOX in the medical treatment of breast cancer.

Acid-sensitive PEG-removable nanoscale liposomes for delivery of doxorubicin in A549/ADR therapy

Hailiang Chen,Chenyu Liu,Simiao Yu,Hengjun Zhou,Farishta Shafiq,Weihong Qiao

Polyethylene glycol (PEG), which can impart long cycling performance to drug carriers, has been commonly used for drug carrier modification. However, PEG modification impedes cellular uptake of drug carriers and intracellular release of drugs, a problem known as the “PEG dilemma” that limits its application. In this study, we designed and synthesized mPEG-NCH-DOB molecules with acid-sensitive hydrazone bonding for the responsive removal of PEG. Drug-loaded lipid PHDGX for doxorubicin (DOX) delivery was obtained by compounding mPEG-NCH-DOB with lipid DOPG, which possess the capability for long cycling, and acid-sensitive PEG-removal to accelerate drug release and enhance cellular uptake. mPEG-NCH-DOB could reach 50% fracture rate after 24 h at pH 5.0. The cytotoxicity assay and flow cytometry (FCM) results showed that PHDGX could enter A549/ADR cells more easily than free DOX at low DOX concentrations and has stronger anti-cancer ability. Through a confocal laser-scanning microscopy (CLSM) study, PHDGX was found to enter the nucleus of A549/ADR cells more easily than free DOX at the same time point, which indicated that PHDGX could overcome the DOX resistance of A549/ADR at low DOX concentrations. The 3D tumor microsphere (MC) growth inhibition assay showed that PHDGX not only has the best MC inhibition ability but also has better MC penetration ability than free DOX. Therefore, this drug-loaded liposome has good stability under conventional conditions and responsive PEG removal in the tumor acid environment, offering a potential strategy for utilizing PEG in drug carrier modification and overcoming tumor resistance to free drugs.

Eupatilin attenuates doxorubicin-induced cardiotoxicity by activating the PI3K-AKT signaling pathway in mice

Lu Yanyu,Min Qianqian,Zhao Xiaoyan,Li Li,Zhao Guojun,Dong Jianzeng

Eupatilin is a pharmacologically active flavonoid with a variety of biological activities, such as anticancer, anti-inflammatory, antioxidant, neuroprotective, anti-allergic and cardioprotective effects. However, whether eupatilin has protective effects on doxorubicin-induced cardiotoxicity remains unknown. Thus, this study aimed to investigate the role of eupatilin in doxorubicin-induced cardiotoxicity. Mice were exposed to a single dose of doxorubicin (15 mg/kg) to generate doxorubicin-induced cardiotoxicity or normal saline as a control. To explore the protective effects, mice were intraperitoneally injected with eupatilin daily for 7 days. Then, we examined the changes in cardiac function, inflammation, apoptosis, and oxidative stress to evaluate the effects of eupatilin on doxorubicin-induced cardiotoxicity. Additionally, RNA-seq analysis was introduced to explore the potential molecular mechanisms. Eupatilin ameliorated doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and cardiomyocyte apoptosis and ameliorated doxorubicin-induced cardiac dysfunction. Mechanistically, eupatilin activated the PI3K-AKT signaling pathway, as evidenced by RNA-seq analysis and Western blot analysis. This study provides the first evidence that eupatilin ameliorates doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and apoptosis. Pharmacotherapy with eupatilin provides a novel therapeutic regimen for doxorubicin-induced cardiotoxicity.

NIR Responsive Doxorubicin-Loaded Hollow Copper Ferrite @ Polydopamine for Synergistic Chemodynamic/Photothermal/Chemo-Therapy

Xiao Chu,Liufang Zhang,Yiling Li,Yue He,Yu Zhang,Chang Du

Osteosarcoma (OS) is the most serious bone malignancy, and the survival rate has not significantly improved in the past 40 years. Thus, it is urgent to develop a new strategy for OS treatment. Chemodynamic therapy (CDT) as a novel therapeutic method can destroy cancer cells by converting endogenous hydrogen peroxide (H 2 O 2 ) into highly toxic hydroxyl radicals (·OH). However, the therapeutic efficacy of CDT is severely limited by the low catalytic efficiency and overexpressed glutathione (GSH). Herein, an excellent nanocatalytic platform is constructed via a simple solvothermal method using F127 as a soft template to form the hollow copper ferrite (HCF) nanoparticle, followed by the coating of polydopamine on the surface and the loading of doxorubicin (DOX). The Fe 3+ and Cu 2+ released from HCF@polydopamine (HCFP) can deplete GSH through the redox reactions, and then trigger the H 2 O 2 to generate ·OH by Fenton/Fenton-like reaction, resulting in enhanced CDT efficacy. Impressively, the photothermal effect of HCFP can further enhance the efficiency of CDT and accelerate the release of DOX. Both in vitro and in vivo experiments reveal that the synergistic chemodynamic/photothermal/chemo-therapy exhibits a significantly enhanced anti-OS effect. This work provides a promising strategy for OS treatment.

Preparation and evaluation of SiO2-deposited stearic acid-g-chitosan nanoparticles for doxorubicin delivery

Hong Yuan,Xin Bao,Yong-Zhong Du,Jian You,Fu-Qiang Hu

Engineered bacteria combined with doxorubicin nanoparticles suppress angiogenesis and metastasis in murine melanoma models

Meiyang Yang,Mariana Conceição,Weijun Chen,Fuwei Yang,Bingke Zhao,Matthew J.A. Wood,Lipeng Qiu,Jinghua Chen

Methods capable of distributing antitumour therapeutics uniformly throughout an entire tumour and that can suppress metastasis at the same time, would be of great significance in improving cancer treatment. Bacteria-mediated synergistic therapies have been explored for better specificity, temporal and spatial controllability, as well for providing regulation of the immune microenvironment, in order to provide improved cancer treatment. To achieve this goal, here we developed an engineered bacteria delivery system ( [email protected] ) using synthetic biology and interfacial chemistry technologies. The engineered bacteria were concurrently modified to express heparin sulfatase 1 (HSulf-1) inside (HSEc), to attach doxorubicin-loaded glycogen nanoparticles (GDOX NPs) on their surface. Here we demonstrate that HSEc can actively target and colonise tumour sites resulting in HSulf-1 overexpression, thereby suppressing angiogenesis and metastasis. Simultaneously, the GDOX NPs were able to penetrate into tumour cells, leading to intracellular DNA damage. Our results confirmed that a combination of biotherapy and chemotherapy using [email protected] resulted in significant melanoma suppression in murine models, with reduced side effects. This study provides a powerful platform for the simultaneous delivery of biomacromolecules and chemotherapeutic drugs to tumours, representing an innovative strategy potentially more effective in treating solid tumours. Statement of significance An original engineered bacteria-based system ( [email protected] ) was developed using synthetic biology and interfacial chemistry technologies to concurrently produce naturally occurring heparin sulfatase 1 (HSulf-1) inside and anchor doxorubicin-loaded glycogen nanoparticles on the surface. [email protected] allowed for combined local delivery of chemotherapeutic agents along with the enzymes and immunostimulatory bacterial adjuvants, which resulted in a synergistic action in the inhibition of tumour growth and metastasis. The study provides a potential therapeutic approach that allows therapeutic agents to be distributed in a spatiotemporally controllable manner in tumours for combinatorial enhanced therapy.

Implantable 3D Printed Hydrogel Scaffolds Loading Copper-Doxorubicin Complexes for Postoperative Chemo/Chemodynamic Therapy

Wentao Dang,Yuqin Wang,Wei-Chih Chen,Enguo Ju,Rachel L. Mintz,Yue Teng,Lili Zhu,Kun Wang,Shixian Lv,Hon Fai Chan,Yu Tao,Mingqiang Li

Biomaterial-based implants hold great potential for postoperative cancer treatment due to the enhanced drug dosage at the disease site and decreased systemic toxicity. However, the elaborate design of implants to avoid complicated chemical modification and burst release remains challenging. Herein, we report a three-dimensional (3D) printed hydrogel scaffold to enable sustained release of drugs for postoperative synergistic cancer therapy. The hydrogel scaffold is composed of Pluronic F127 and sodium alginate (SA) as well as doxorubicin (DOX) and copper ions (F127-SA/Cu-DOX hydrogel scaffold). Benefiting from the coordination of Cu(II) with both SA and DOX, burst release of DOX can be overcome, and prolonged release time can be achieved. The therapeutic efficiency can be adjusted by altering the amount of DOX and Cu(II) in the scaffolds. Moreover, apoptosis and ferroptosis of cancer cells can be induced through the combination of chemotherapy and chemodynamic therapy. In addition, DOX supplies excess hydrogen peroxide to enhance the efficiency of Cu-based chemodynamic therapy. When implanted in the resection site, hydrogel scaffolds effectively inhibit tumor growth. Overall, this study may offer a new strategy for fabricating local implants with synergistic therapeutic performance for preventing postoperative cancer recurrence.

Plasma Pharmacokinetics and Tissue Distribution of Doxorubicin in Rats following Treatment with Astragali Radix

Yin Huang,Fang Yang,Linling Guo,Yan Xu,Xiaxia Yu,Zunjian Zhang,Yuxin Zhang

Doxorubicin (DOX) is an essential component in chemotherapy, and Astragali Radix (AR) is a widely used tonic herbal medicine. The combination of DOX and AR offers widespread, well-documented advantages in treating cancer, e.g., reducing the risk of adverse effects. This study mainly aims to uncover the impact of AR on DOX disposition in vivo. Rats received a single intravenous dose of 5 mg/kg DOX following a single-dose co-treatment or multiple-dose pre-treatment of AR (10 g/kg × 1 or × 10). The concentrations of DOX in rat plasma and six tissues, including heart, liver, lung, kidney, spleen, and skeletal muscle, were determined by a fully validated LC-MS/MS method. A network-based approach was further employed to quantify the relationships between enzymes that metabolize and transport DOX and the targets of nine representative AR components in the human protein–protein interactome. We found that short-term (≤10 d) AR administration was ineffective in changing the plasma pharmacokinetics of DOX in terms of the area under the concentration–time curve (AUC, 1303.35 ± 271.74 μg/L*h versus 1208.74 ± 145.35 μg/L*h,p> 0.46), peak concentrations (Cmax, 1351.21 ± 364.86 μg/L versus 1411.01 ± 368.38 μg/L,p> 0.78), and half-life (t1/2, 31.79 ± 5.12 h versus 32.05 ± 6.95 h,p> 0.94), etc. Compared to the isotype control group, DOX concentrations in six tissues slightly decreased under AR pre-administration but only showed statistical significance (p< 0.05) in the liver. Using network analysis, we showed that five of the nine representative AR components were not localized to the vicinity of the DOX disposition-associated module. These findings suggest that AR may mitigate DOX-induced toxicity by affecting drug targets rather than drug disposition.Keywords:Adriamycin;drug disposition;combination therapy;LC-MS/MS;network

Preparation of pH-responsive solanesol-based poly (glutamic acid) micellar carrier for doxorubicin delivery

Hua Yuan,Liming Zhou,Zhiwen Qi,Changwei Zhang,Chengzhang Wang

This study focuses on the development of a new preparation method of solanesol derivatives for their effective use as drug carriers. The current preparation methods for solanesol derivatives generally suffer from poor accessibility and low yields of the target products, which affect the further development of their products. To address this issue, a solanesol-based poly (glutamic acid) (Sol-PEG-PGA) was first designed on the basis of the click reaction between alkynyl-functionalized solanesol and amino-polyethylene glycol (PEG)-azide, followed by a coupling reaction with poly (glutamic acid). The introduced polyethylene glycol and poly (glutamic acid) conferred amphipathic properties on solanesol. Sol-PEG-PGA possessed a suitable lipid-water partition coefficient of 1.01 and water contact angle of 55° and could self-assemble into spherical micelles with an average diameter of 74.0 ± 3.5 nm to load doxorubicin (DOX) via hydrophobic interaction, with a loading capacity of 27.7 ± 1.2 %. Besides, Sol-PEG-PGA micelle exhibited excellent stability before and after loading DOX under the dilution of 1000 times and could be stored stably at room temperature for 15 days. The DOX loaded into Sol-PEG-PGA could be released by acid induction, with a cumulative release of 84.8 ± 2.5 % at pH 5.0. Furthermore, in vitro cytotoxicity assay, the normal cells NIH/3T3 treated with Sol-PEG-PGA maintained relatively high viability of 95.0% compared to that of free DOX at 320 µg/mL, verifying its good biocompatibility. The DOX loaded into Sol-PEG-PGA possessed a high-efficiency anticancer activity compared to free DOX, with an inhibition rate of 99.2 ± 1.6 % against tumor cells 4T1, suggesting the potentials of Sol-PEG-PGA for drug delivery applications. This new preparation method is expected to provide a new strategy for constructing various functional carriers from solanesol derivatives.

Delivery of doxorubicin by dual responsive carboxymethyl chitosan based nanogel and in vitro performance

Lianlian Yang,Junhong Ling,Nan Wang,Yongjun Jiang,Yuqing Lu,Li-Ye Yang,Xiao–kun Ouyang

Here, glycidyl methacrylate (GMA) was used for modification of carboxymethyl chitosan (CMCS). The double bond on the side group of CMCS was polymerized and cross-linked with N-N′-bis(acryloyl) cysteamine (BAC), containing a disulfide bond, and modified with folic acid (FA) to obtain nanogels for the targeted delivery of doxorubicin (DOX). Effectiveness of DOX delivery and release were subsequently investigated. The drug encapsulation efficiency (EE) and loading capacity (LC) of DOX were 94.77 ± 0.83% and 15.6 ± 0.12%, respectively. The particle size of the GCMCS-FA-DOX nanoparticles loaded with DOX was 220.4 ± 38.4 nm. The experimental results showed that GCMCS-FA-DOX had a high glutathione and pH response performance. GCMCS-FA-DOX showed an improved inhibitory effect on tumor cell proliferation compared to free DOX. GCMCS-FA-DOX significantly improved the efficiency of drug uptake by cells, and the cytotoxicity of GCMCS-FA-DOX in HCT-116 tumor cells was higher than that in HepG-2 tumor cells.

Construction and Biological Evaluation of Multiple Modification Hollow Mesoporous Silicone Doxorubicin Nanodrug Delivery System

Hu Mengru,Zhang Wenjing,Chen Weidong,Chen Yunna,Huang Qianqian,Bao Qianqian,Lin Tongyuan,Wang Lei,Zhang Shantang

Abstract. The combination of functionalized nanoparticles and chemotherapy drugs can effectively target tumor tissue, which can improve efficacy and reduce toxicity. In this article, pPeptide-PDA@HMONs-DOX nanoparticles (phosphopeptide-modified polydopamine encapsulates doxorubicin-loaded hollow mesoporous organosilica nanoparticles) were constructed that based on multiple modification hollow mesoporous organosilica nanoparticles (HMONs). The pPeptide-PDA@HMONs-DOX nanoparticles retain the biological functions of phosphorylated peptide while exhibiting biological safety that are suitable for effective drug delivery and stimulus responsive release. The degradation behaviors showed that pPeptide-PDA@HMONs-DOX has dual-responsive to drug release characteristics of pH and glutathione (GSH). In addition, the prepared pPeptide-PDA@HMONs-DOX nanoparticles have good biological safety, and their anti-tumor efficacy was significantly better than doxorubicin (DOX). This provided new research ideas for the construction of targeted nanodrug delivery systems based on mesoporous silicon. Graphical Abstract Scheme 1 The preparation of pPeptide-PDA@HMONs-DOX and the process of drug release under multiple responses. (A) Schematic diagram of the synthesis process of pPeptide-PDA@HMONs-DOX. (B) The process in which nanoparticles enter the cell and decompose and release DOX in response to pH and GSH

Phloretin alleviates doxorubicin-induced cardiotoxicity through regulating Hif3a transcription via targeting transcription factor Fos

Xiangyun Li,Taoli Sun,Jiaqin Liu,Shanshan Wei,Yuanying Yang,Jian Liu,Bikui Zhang,Wenqun Li

Background Doxorubicin (Dox), a chemotherapeutic agent known for its efficacy, has been associated with the development of severe cardiotoxicity, commonly referred to as doxorubicin-induced cardiotoxicity (DIC). The role and mechanism of action of phloretin (Phl) in cardiovascular diseases are well-established; however, its specific function and underlying mechanism in the context of DIC have yet to be fully elucidated. Objective This research aimed to uncover the protective effect of Phl against DIC in vivo and in vitro , while also providing a comprehensive understanding of the underlying mechanisms involved. Methods DIC cell and murine models were established. The action targets and mechanism of Phl against DIC were comprehensively examined by systematic network pharmacology, molecular docking, transcriptomics technologies, transcription factor (TF) prediction, and experimental validation. Results Phl relieved Dox-induced cell apoptosis in vitro and in vivo . Through network pharmacology analysis, a total of 554 co-targeted genes of Phl and Dox were identified. Enrichment analysis revealed several key pathways including the PI3K-Akt signaling pathway, Apoptosis, and the IL-17 signaling pathway. Protein-protein interaction (PPI) analysis identified 24 core co-targeted genes, such as Fos, Jun, Hif1a, which were predicted to bind well to Phl based on molecular docking. Transcriptomics analysis was performed to identify the top 20 differentially expressed genes (DEGs), and 202 transcription factors (TFs) were predicted for these DEGs. Among these TFs, 10 TFs (Fos, Jun, Hif1a, etc.) are also the co-targeted genes, and 3 TFs (Fos, Jun, Hif1a) are also the core co-targeted genes. Further experiments validated the finding that Phl reduced the elevated levels of Hif3a (one of the top 20 DEGs) and Fos (one of Hif3a's predicted TFs) induced by Dox. Moreover, the interaction between Fos protein and the Hif3a promoter was confirmed through luciferase reporter assays. Conclusion Phl actively targeted and down-regulated the Fos protein to inhibit its binding to the promoter region of Hif3a, thereby providing protection against DIC.