Overcoming methotrexate resistance in breast cancer tumour cells by the use of a new cell-penetrating peptide

Lindgren, Maria; Rosenthal-Aizman, Katri; Saar, Külliki; Eiríksdóttir, Emelía; Jiang, Yang; Sassian, Meeri; Östlund, Pernilla; Hällbrink, Mattias; Langel, Ülo

doi:10.1016/j.bcp.2005.10.048

Cited by 182 publications

(97 citation statements)

References 36 publications

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“…M918 efficiently translocated into HeLa and human breast cancer cells, in a nontoxic manner up to concentrations of 25 lM (17). Another CPP, YTA2, developed by Lindgren et al (61) has also been shown to deliver proteins into tumor cells with high efficiency and without exhibiting cytotoxicity at high concentration.…”

Section: Cytotoxicity and Cell Functionmentioning

confidence: 99%

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

2010

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SummaryNovel classes and applications of cell-penetrating peptides (CPPs) are being constantly discovered since they were first identified 2 decades ago. These short cationic peptides (nanomolecules) either by covalent binding or by noncovalent binding can traverse cell membranes and deliver a variety of molecules that are unable to overcome the permeability barrier in their own capacity. The ability of the CPPs to deliver variety of macromolecules, such as oligonucleotides, therapeutic drugs, proteins, and medical imaging agents, by forming nanoparticulate carriers in a range of cells has led them to emerge as a potential tool for both macromolecule delivery application and to gain insight into the fundamentals of mechanism of cellular uptake across the plasma membrane. This review explores the recent advances, challenges, and future prospects in the field of CPP-mediated cargo delivery in mammalian and plant cells. Studies have been conducted into the peptide chemistry and stability of CPP-macromolecular complexes. Most of the CPPs have been shown to be nontoxic and do not interfere with the functionality of the macromolecules delivered across the cell membrane. The mechanism of uptake of CPP-cargo complexes and the uptake of CPPs alone across the plasma membrane remains unresolved. As the world of CPPs is rapidly advancing in both mammalian and plant system, there is a promising future for the various applications of transduction and transfection into intact cells.

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Section: Cytotoxicity and Cell Functionmentioning

confidence: 99%

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

2010

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“…Il apparaît que le couplage de la doxorubicine à un CPP favoriserait en réalité plutôt des mécanismes d'apoptose, différant en ce point du mécanisme traditionnel de mort induite par la doxorubicine seule. Ces résultats obtenus avec la maurocalcine ont pu être généralisés à d'autres CPP [37,38], voire à d'autres agents antitumoraux comme le méthotrexate [39]. D'autres stratégies ont été utilisées [11,28].…”

Section: Délivrer Des Agents Antitumorauxunclassified

Administration de molécules actives dans les cellules

Poillot

Waard

2011

Med Sci (Paris)

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“…Moreover, drug delivery systems can avoid multi drug resistance (MDR) created through factors such as Pglycoprotein and multi drug resistance proteins (MRPs) [12,13,14,15,16,17]. Chemical conjugation with a parent drug as "Prodrug" strategy is one of the drug delivery systems that has been widely used in EPR delivery [12].…”

Section: Introductionmentioning

confidence: 99%

“…These bioactive and biodegradable peptides are able to carry and deliver their cargoes such as nucleic acids, proteins, drugs, or imaging agents, to the cytoplasm or nuclei of cells [29,32,33,34]. In the recent years, numerous natural and synthetic CPPs such as polyarginines, TAT (trans-acting activator of transcription) [26] and peptide amphiphiles (PA) [22] have improved the cellular uptake of various drugs such as Taxol [35], methotrexate [16], and doxorubicin [12]. Among these CPPs, peptide amphiphiles appear to be among efficient systems in drug delivery [36,37,38].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity

Mohammadi

Zakeri–Milani

Golkar

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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A new class of cell penetrating peptides (CPPs) named peptide amphiphile was designed to improve the intracellular uptake and antitumor activity of epirubicin (EPR). Various amphiphilic CPPs were synthesized by solid phase peptide synthesis method and were chemically conjugated to EPR. Their corresponding nanoparticles (CPPs-E4 and CPPs-E8)were prepared via non-covalent binding of the peptides and polyanions. Cytotoxicity and anti-proliferative activity were evaluated by MTT assay. Cellular uptake was examined by flow cytometry and fluorescence microscopy. The CPPs exhibited slight cytotoxicity.Binding of polyglutamate to CPPs (CPPs-E4 and CPPs-E8 nanoparticles) decreased their cytotoxicity. CPPs-E8 nanoparticles showed lower cytotoxicity than CPPs-E4 nanoparticles.Cellular uptake of K3W4K3-E8, K2W4K2-E8 and W3K4W3-E8 reached 100% with no difference between each of the mentioned CPPs and its nanoparticle at 50 µM. The antiproliferative activity of EPR was enhanced following conjugation to peptides and nanoparticles at 25 µM. CPPs-EPR-E4 and -E8 nanoparticles displayed higher antiproliferative activity than CPPs-EPR at 25 µM. CPPs-E8-EPR nanoparticles showed higher anti-proliferative activity than CPPs-E4-EPR. K3W4K3-E8-EPR nanoparticles exhibited the highest anti-proliferative activity at 25 µM. The synthesized peptide nanoparticles are proposed as suitable carriers for improving the intracellular delivery of EPR into tumor cells with low cytotoxicity and high antitumor activity.

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Overcoming methotrexate resistance in breast cancer tumour cells by the use of a new cell-penetrating peptide

Cited by 182 publications

References 36 publications

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

Administration de molécules actives dans les cellules

Synthesis and cellular characterization of various nano-assemblies of cell penetrating peptide-epirubicin-polyglutamate conjugates for the enhancement of antitumor activity

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