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聚电解质羧甲基纤维素增强多柔比星在 MCF7 乳腺癌细胞中的递送:小鼠模型中的毒理学评价。

Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model.

机构信息

Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.

Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

Pharm Res. 2019 Mar 18;36(5):68. doi: 10.1007/s11095-019-2598-3.


DOI:10.1007/s11095-019-2598-3
PMID:30887127
Abstract

PURPOSE: Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems. METHODS: A polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues. RESULTS: The physicochemical properties of developed nanocarrier showed that it can be used in drug delivery purposes. The efficiency of the delivery system was assessed by loading and release studies. Besides, biological assays including protein-particle interaction, hemolysis assay, cytotoxicity study, cellular uptake, and apoptosis analysis were performed. All results persuaded us to investigate the cytotoxic effects of nanocarrier in an animal model by determining the biochemical parameters attributed to organ injuries, and hematoxylin and eosin (H&E) staining for histopathological manifestations. We observed that the nanocarrier has no toxic effect on healthy tissues, while, it is capable of reducing the toxic side effects of doxorubicin by more cellular internalization. CONCLUSION: Chemical characterizations and biological studies confirmed that developed nanocarrier with permanent cationic groups of imidazolium and anionic carboxylic acid groups is an effective candidate for anticancer drug delivery.

摘要

目的:化疗作为癌症治疗的重要手段,面临着多药耐药性和对健康组织产生不良毒性作用等诸多障碍。药物传递系统为克服这些问题开辟了新的途径。

方法:合成了一种聚电解质羧甲基纤维素聚合物作为磁性纳米载体,以增强阿霉素在 MCF7 乳腺癌细胞中的传递和摄取,并降低对健康组织的不良毒性作用。

结果:所开发的纳米载体的物理化学性质表明它可用于药物传递目的。通过载药和释放研究评估了递药系统的效率。此外,还进行了包括蛋白-颗粒相互作用、溶血试验、细胞毒性研究、细胞摄取和细胞凋亡分析在内的生物学测定。所有结果都促使我们通过确定与器官损伤相关的生化参数,并进行苏木精和伊红(H&E)染色以观察组织病理学表现,在动物模型中研究纳米载体的细胞毒性作用。我们观察到,纳米载体对健康组织没有毒性作用,而它能够通过更多的细胞内化来减少阿霉素的毒性副作用。

结论:化学特性和生物学研究证实,具有永久性阳离子咪唑基团和阴离子羧酸基团的开发型纳米载体是一种有效的抗癌药物传递候选物。

相似文献

[1]
Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model.

Pharm Res. 2019-3-18

[2]
Needle-shaped amphoteric calix[4]arene as a magnetic nanocarrier for simultaneous delivery of anticancer drugs to the breast cancer cells.

Int J Nanomedicine. 2019-4-15

[3]
Synthesis of biocompatible nanocrystalline cellulose against folate receptors as a novel carrier for targeted delivery of doxorubicin.

Chem Biol Interact. 2022-1-5

[4]
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J Biomater Sci Polym Ed. 2017-12-15

[5]
Chitosan Immobilization on Bio-MOF Nanostructures: A Biocompatible pH-Responsive Nanocarrier for Doxorubicin Release on MCF-7 Cell Lines of Human Breast Cancer.

Inorg Chem. 2018-10-17

[6]
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[7]
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[8]
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Colloids Surf B Biointerfaces. 2017-5-1

[9]
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Int J Pharm. 2016-3-30

[10]
Magnetic pH-responsive nanocarrier with long spacer length and high colloidal stability for controlled delivery of doxorubicin.

Colloids Surf B Biointerfaces. 2013-12-30

引用本文的文献

[1]
Harnessing polyelectrolyte complexes for precision cancer targeting: a comprehensive review.

Med Oncol. 2024-5-10

[2]
A Lysine-Functionalized Graphene Oxide-Based Nanoplatform for Delivery of Fluorouracil to A549 Human Lung Cancer Cells: A Comparative Study.

Tanaffos. 2021-4

[3]
Spherical Cellulose Micro and Nanoparticles: A Review of Recent Developments and Applications.

Nanomaterials (Basel). 2021-10-17

[4]
Synthesis, Crystal Structure, and Biological Activity of a Multidentate Calix[4]arene Ligand Doubly Functionalized by 2-Hydroxybenzeledene-Thiosemicarbazone.

Molecules. 2020-1-16

本文引用的文献

[1]
Multi-branched ionic liquid-chitosan as a smart and biocompatible nano-vehicle for combination chemotherapy with stealth and targeted properties.

Carbohydr Polym. 2018-5-18

[2]
Reversion of Multidrug Resistance by Co-Encapsulation of Doxorubicin and Metformin in Poly(lactide-co-glycolide)-d-α-tocopheryl Polyethylene Glycol 1000 Succinate Nanoparticles.

Pharm Res. 2018-4-18

[3]
Suppression of p53R2 gene expression with specific siRNA sensitizes HepG2 cells to doxorubicin.

Gene. 2018-2-5

[4]
Metformin enhances doxorubicin sensitivity via inhibition of doxorubicin efflux in P-gp-overexpressing MCF-7 cells.

Chem Biol Drug Des. 2017-8-24

[5]
New insights into antidiabetic drugs: Possible applications in cancer treatment.

Chem Biol Drug Des. 2017-12

[6]
Modulating tumor hypoxia by nanomedicine for effective cancer therapy.

J Cell Physiol. 2018-3

[7]
Anthracycline Chemotherapy and Cardiotoxicity.

Cardiovasc Drugs Ther. 2017-2

[8]
An Evaluation of Blood Compatibility of Silver Nanoparticles.

Sci Rep. 2016-5-5

[9]
Poly (acrylic acid sodium) grafted carboxymethyl cellulose as a high performance polymer binder for silicon anode in lithium ion batteries.

Sci Rep. 2016-1-20

[10]
Differential effects of peroxisome proliferator-activated receptor agonists on doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells.

Cell Mol Biol (Noisy-le-grand). 2015-12-30

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