Enhancement of anti-tumor activity of hybrid peptide in conjugation with carboxymethyl dextran via disulfide linkers

Gaowa, Arong; Horibe, Tomohisa; Kohno, Masayuki; Tabata, Yasuhiko; Harada, Hiroshi; Hiraoka, Masahiro; Kawakami, Koji

doi:10.1016/j.ejpb.2015.03.015

Cited by 19 publications

(18 citation statements)

References 35 publications

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“…This carrier material was used as the polymer material to prepare the nanoparticles, and the PEG on its surface may ensure the nanoparticles to retain their EPR and enable them to reach to the focus as soon as possible through the venous blood [ 21 , 22 , 23 ]. The ECA with disulfide bonds designed in this study was aimed at the dissociation of ECA in the highly expressed GSH environment in tumor cells to make the ECA exert its effect as a GST inhibitor to reduce the multidrug resistance of tumor cells [ 24 , 25 ]. Due to more active groups of the ECA, the synthetic reaction at the ECA end should be minimized as far as possible.…”

Section: Resultsmentioning

confidence: 99%

Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma

Han

Wang²,

Wang

et al. 2015

Nanomaterials

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During the chemotherapy of cancer, drug resistance is the first issue that chemotherapeutic drugs cannot be effectively used for the treatment of cancers repeatedly for a long term, and the main reason for this is that tumor cell detoxification is mediated by GSH (glutathione) catalyzed by GST (glutathione-S-transferase). In this study, a GST inhibitor, ethacrynic acid (ECA), was designed to be coupled with methoxy poly(ethylene glycol)-poly(lactide) (MPEG–PLA) by disulfide bonds to prepare methoxy poly(ethylene glycol)-poly(lactide)-disulphide bond-mthacrynic acid (MPEG–PLA–SS–ECA) as a carrier material of the nanoparticles. Nanoparticles of pingyangmycin (PYM) and carboplatin (CBP) were prepared, respectively, and their physicochemical properties were investigated. The ECA at the disulfide could be released in the presence of GSH, the pingyangmycin, carboplatin and ECA were all uniformly released, and the nanoparticles could release all the drugs completely within 10 days. The half maximal inhibitory concentration (IC50) of the prepared MPEG–PLA–SS–ECA/CBP and MPEG–PLA–SS–ECA/PYM nanoparticles in drug-resistant oral squamous cell carcinoma cell lines SCC15/CBP and SCC15/PYM cells was 12.68 μg·mL−1 and 12.76 μg·mL−1, respectively; the resistant factor RF of them in the drug-resistant cells were 1.51 and 1.24, respectively, indicating that MPEG–PLA–SS–ECA nanoparticles can reverse the drug resistance of these two drug-resistant cells.

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Section: Resultsmentioning

confidence: 99%

Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma

Han

Wang²,

Wang

et al. 2015

Nanomaterials

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“…Disulfide bonds have been incorporated in the synthesis of cleavable delivery systems for DNA, RNA, and siRNA [117–121], antisense oligonucleotides [122], peptides [123], toxins [124] and anticancer drugs [125–127]. An interesting design is the dynamic conjugates that combine endosomolytic function with siRNA reductive release [77,128,129].…”

Section: Design Principles For Water-soluble Polymer-drug Conjugatesmentioning

confidence: 99%

Design of smart HPMA copolymer-based nanomedicines

Yang

Kopeček

2016

Journal of Controlled Release

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The state-of-the art in water-soluble macromolecular therapeutics has been reviewed. First the design principles for polymer-drug conjugates are discussed followed by two recent developments in the field: a) The design, synthesis and properties of backbone degradable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates. The enhanced intravascular half-life of such conjugates creates a concentration gradient (blood vs. tumor) for an extended time interval resulting in increased solid tumor accumulation by enhanced permeability and retention (EPR) effect with concomitant increase in efficacy. b) Drug-free macromolecular therapeutics is a new paradigm in macromolecular therapeutics. Apoptosis in malignant cell is induced by crosslinking of cell surface non-internalizing receptors. Crosslinking of receptors is mediated by the biorecognition of two nanoconjugates containing high-fidelity complementary motifs (peptides or oligonucleotides). Results for the treatment of B cell lymphomas in animal models and patient cells demonstrate the high translational potential of this aproach.

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“…This activity was demonstrated in vitro and in vivo in a mouse xenograft model against pancreatic, colon, lung, esophageal, oral, ovary, and breast cancer cells, and head and neck squamous cell carcinoma. We also demonstrated the efficacy of hybrid peptides as a drug delivery system using the EGFR2R–lytic peptide via its combination with a biodegradable gelatin hydrogel and carboxymethyl dextran via disulfide linkers in vitro and in vivo (Gaowa et al., , ). Our previous finding that no T‐cell immune response or antibodies were detected in a mouse model treated with the hybrid peptide (Kawamoto, Kohno, Horibe, & Kawakami, ) suggests that the use of the hybrid peptide might have overcome the problems associated with the administration of recombinant protein drugs, such as immunotoxins.…”

Section: Introductionmentioning

confidence: 98%

A novel interleukin‐13 receptor alpha 2‐targeted hybrid peptide for effective glioblastoma therapy

et al. 2019

Self Cite

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We previously designed and reported a novel class of drugs, namely hybrid peptides, which are chemically synthesized and composed of a targeted binding peptide and a lytic‐type peptide containing cationic amino acid residues that cause cancer cell death. In the present study, we screened for peptides that bind to interleukin‐13 receptor alpha 2 (IL‐13Rα2) by using a T7 random peptide phage display library system and isolated several positive phage clones. The A2b11 peptide, which was one of the positive clones, was shown to bind to IL‐13Rα2 protein by Biacore analysis and a binding assay using glioblastoma (GB) cell lines. This peptide was linked with a lytic peptide containing a linker sequence to form the IL‐13Rα2–lytic hybrid peptide. The IL‐13Rα2–lytic hybrid peptide showed cytotoxic activity against GB cell lines in vitro. The IL‐13Rα2–lytic hybrid peptide also affected Akt and Erk1/2 activation following treatment with interleukin‐13 and induced rapid ATP dynamics in GB cells. Anti‐tumor activity of the IL‐13Rα2–lytic hybrid peptide was observed in vivo after intratumoral injection in a mouse xenograft model of human GB cells. These results suggest that the IL‐13Rα2–lytic hybrid peptide might be a potent therapeutic option for patients with GB.

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Enhancement of anti-tumor activity of hybrid peptide in conjugation with carboxymethyl dextran via disulfide linkers

Cited by 19 publications

References 35 publications

Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma

Preparation of GST Inhibitor Nanoparticle Drug Delivery System and Its Reversal Effect on the Multidrug Resistance in Oral Carcinoma

Design of smart HPMA copolymer-based nanomedicines

A novel interleukin‐13 receptor alpha 2‐targeted hybrid peptide for effective glioblastoma therapy

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