Chemosensitization of doxorubicin in multidrug-resistant cells by unimolecular micelles via increased cellular accumulation and apoptosis

Wang, Meng; Han, Min; Liu, Ying; Jin, Yi

doi:10.1111/jphp.12528

Cited by 21 publications

(4 citation statements)

References 35 publications

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“…These results are in agreement with those recently obtained with MCF-7/ADR cells treated with doxorubicin loaded in F127-attached polyamidoamine (PAMAM) dendrimer conjugates. [22] According to the IC 50 values recorded in such study, as much as a 33fold increase in drug sensitivity was observed, undoubtedly showing that this compound strongly displayed the reversal effect of drug resistance. Furthermore, Western blot analysis demonstrated that this PEO-PPO surfactant is able to overcome MDR by inhibiting BCRP at the expression level.…”

Section: Discussionmentioning

confidence: 75%

“…Results showed that in the presence of Pluronic ® F127, doxorubicin exhibited a considerable decrease in IC 50 that lead to CEI values, indicating an increase in drug sensitivity from 9‐ to 41‐fold, according to both the analysed cell line as well as the copolymer concentration. These results are in agreement with those recently obtained with MCF‐7/ADR cells treated with doxorubicin loaded in F127‐attached polyamidoamine (PAMAM) dendrimer conjugates . According to the IC 50 values recorded in such study, as much as a 33‐fold increase in drug sensitivity was observed, undoubtedly showing that this compound strongly displayed the reversal effect of drug resistance.…”

Section: Discussionmentioning

confidence: 98%

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F127 poloxamer effect on cytotoxicity induction of tumour cell cultures treated with doxorubicin

Gentile

Castronuovo

Cuestas

et al. 2019

Journal of Pharmacy and Pharmacology

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Introduction Hepatocellular carcinoma is the most common liver malignancy and the third leading cause of cancer death worldwide. One crucial limitation in the pharmacotherapy for this tumour is its chemotherapy‐resistant nature produced by the overexpression of several members of the ATP‐binding cassette protein family that efflux drugs out of cells, as observed with the breast cancer resistant protein (BCRP). Objectives This study aimed to assess the ability of Pluronic® F127 to reverse the multidrug resistance phenotype in two human hepatocellular cell lines. Methods PLC/PRF/5 and SKHep1 cells were exposed to Pluronic® F127 at several concentrations. The effect of F127 on BCRP expression (mRNA and protein), mitochondrial transmembrane potential and cell hypodiploidy was assessed. Finally, the effect of this copolymer on cytotoxicity of doxorubicin in both hepatoma cell lines was investigated, as expressed by its reverse resistance index. Key findings It was demonstrated that F127 in both cell lines contributes to chemosensitization, as shown by BCRP down‐regulation, an altered mitochondrial transmembrane potential and hypodiploidy and reverse resistance index values. A remarkable dependence of these effects significantly correlated with the copolymer concentration. Conclusions These findings further uncover the potential usefulness of this copolymer as multidrug resistance reversal agent, increasing the efficacy of cancer therapies.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 98%

F127 poloxamer effect on cytotoxicity induction of tumour cell cultures treated with doxorubicin

Gentile

Castronuovo

Cuestas

et al. 2019

Journal of Pharmacy and Pharmacology

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“…Several studies have reported that doxorubicin induces apoptosis by activating caspases and disrupting the mitochondrial membrane potential [56,57]. A study of the cell death pathway depending on incubation both with the phospholipid system itself and with its components separately showed that death was predominantly apoptotic in all variants.…”

Section: Discussionmentioning

confidence: 99%

Effect of an NGR Peptide on the Efficacy of the Doxorubicin Phospholipid Delivery System

Kostryukova,

Tereshkina,

Tikhonova

et al. 2023

Nanomaterials

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This study is a continuation of an investigation into the effect of a targeted component, a peptide with an NGR, on the properties of the previously developed doxorubicin phospholipid delivery system. The NGR peptide has an affinity for aminopeptidase N (known as the CD13 marker on the membrane surface of tumor cells) and has been extensively used to target drug delivery systems. This article presents the results of a study investigating the physical properties of the phospholipid composition with and without the peptide chain: particle size, zeta potential, stability in fluids, and dependence of doxorubicin release from nanoparticles at different pH levels (5.0, 6.5, 7.4). The cytotoxic effect of the compositions has also been shown to depend on the dose of the drug used for incubation, the presence of the targeted component in the composition, and the time of incubation time of the substances. There was a significant difference in the cytotoxic effect on HT-1080 (CD13-positive) and MCF-7 (CD13-negative) cells. Cell death pathway analysis has shown that death occurred mainly by apoptosis. We also present data on the effect of doxorubicin embedded in phospholipid nanoparticles with the targeted peptide on DNA assessed by differential pulse voltammetry, the mechanism of action being electrostatic interactions. The interactions of native dsDNA with doxorubicin encapsulated in phospholipid nanoparticles with the targeted peptide were studied electrochemically by differential pulse voltammetry. Here, we have highlighted that the targeted peptide in the doxorubicin composition moved specific interaction of the drug with dsDNA from intercalative mode to electrostatic interactions.

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“…Nevertheless, conventional dosage forms lack selective targeting and deep penetration, resulting in severe systemic toxicity and an inefficient lethal threshold. Therefore, nanoparticles are the most explored vehicles to combat MDR 6 , 13 - 15 , including liposomes 16 , 17 , micelles 18 , 19 , gold nanoparticles 20 , 21 , magnetic nanoparticles 22 , 23 , carbon nanotubes 24 , 25 , dendrimers 26 , mesoporous silica nanoparticles 27 , 28 etc. These nanoparticles can deliver agents either chemically grafted or physically encapsulated specifically to cancer cells 29 , taking advantage of the enhanced permeability and retention (EPR) effect in the tumor and ligand-receptor-mediated active targeting.…”

Section: Introductionmentioning

confidence: 99%

Stimuli-Responsive Nanomedicines for Overcoming Cancer Multidrug Resistance

2018

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Chemotherapy is still a main option for cancer therapy, but its efficacy is often unsatisfying due to multidrug resistance (MDR). The tumor microenvironment is considered a dominant factor causing MDR. Stimuli-responsive nanomedicines exhibit many superiorities for reversal of MDR. As smart systems, stimuli-responsive nanomedicines are desirable for achieving site-specific accumulation and triggered drug release in response to slight changes in physicochemical properties in pathological conditions or to exogenous stimuli. In this review, we highlight the current progress of various nanomedicines with different stimuli-responsive capabilities for overcoming MDR. The materials, design, construction as well as efficacy in overcoming MDR of these nanomedicines are discussed. Eventually, we look forward to forthcoming intelligent nanoparticle systems with new mechanisms to deliver drugs for practical applications in conquering cancer MDR.

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Chemosensitization of doxorubicin in multidrug-resistant cells by unimolecular micelles via increased cellular accumulation and apoptosis

Abstract: PF127-PAMAM conjugates showed superiority in the treatment of MCF-7/ADR, which implied the potential vehicles of anticancer drugs for the reversal of MDR.

Cited by 21 publications

References 35 publications

F127 poloxamer effect on cytotoxicity induction of tumour cell cultures treated with doxorubicin

F127 poloxamer effect on cytotoxicity induction of tumour cell cultures treated with doxorubicin

Effect of an NGR Peptide on the Efficacy of the Doxorubicin Phospholipid Delivery System

Stimuli-Responsive Nanomedicines for Overcoming Cancer Multidrug Resistance

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