EGFR-targeted poly(ethylene glycol)-distearoylphosphatidylethanolamine micelle loaded with paclitaxel for laryngeal cancer: preparation, characterization and<i>in vitro</i>evaluation

Ren, Henglei; Gao, Chunli; Zhou, Liang; Liu, Min; Xie, Conghua; Lu, Weiyue

doi:10.3109/10717544.2014.896057

Cited by 28 publications

(12 citation statements)

References 46 publications

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“…In combination with the results of gene transfection in vitro and in vivo, the GE11 modification was believed to be the main reason for the high transfection efficiency in gene delivery using PEG-PEI. This was consistent with our previous study showing that the GE11-PEG-DSPE micelle could deliver more paclitaxel to Hep-2 cells [9]. Future intensive studies should be performed to explore the potential of co-delivering GE11-modified chemotherapeutic agents and genes for laryngeal cancer therapy.…”

Section: Discussionsupporting

confidence: 91%

“…GE11 peptide specifically and efficiently binds to EGFR with a much lower mitogenic activity than that of EGF [7,8]. In a previous study, we reported the use of GE11-modified polyethylene glycol-distearoyl-phosphatidylethanolamine (PEG-DSPE) micelle and demonstrated that our targeted micelle approach results in enhanced intracellular delivery and therefore improved paclitaxel cytotoxicity on the EGFR-overexpressing human laryngeal cancer cell line Hep-2 [9]. For gene delivery systems, GE11-conjugated PEI vectors remain quite efficient for transfecting genes into hepatoma cells and tumor xenografts that highly express EGFR [7].…”

Section: Introductionmentioning

confidence: 93%

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Peptide GE11–Polyethylene Glycol–Polyethylenimine for targeted gene delivery in laryngeal cancer

et al. 2015

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The objective of this study was to evaluate the possibility of using GE11-polyethylene glycol-polyethylenimine (GE11-PEG-PEI) for targeted gene delivery to treat epidermal growth factor receptor (EGFR)-overexpressing laryngeal cancer. This study described the design, characterization, and in vitro and in vivo study of the nanocarrier GE11-PEG-PEI for gene delivery to treat laryngeal cancer. Analysis of the sizes and zeta potentials indicated that the formation of PEGylated complexes was dependent on the N/P ratio, and these complexes were capable of binding plasmid DNA and condensing DNA into small positively charged nanoparticles. The results also revealed that GE11-PEG-PEI had a weaker effect on cell survival in vitro. Gene transfection was performed on human laryngeal cancer Hep-2 cells in vitro and in vivo. Both the in vitro and in vivo results demonstrated that GE11-PEG-PEI had greater transfection efficiency than mPEG-PEI. Compared with mPEG-PEI/pORF-hTRAIL and saline, GE11-PEG-PEI/pORFh-TRAIL significantly (p < 0.05) reduced tumor growth in nude mice with laryngeal cancer. Moreover, the GE11-PEG-PEI/pORF-hTRAIL-treated groups showed more apoptosis than the mPEG-PEI/pORF-hTRAIL-treated groups. Therefore, our results showed that the peptide GE11 conjugated to PEG-PEI delivered significantly more genes to EGFR-overexpressing laryngeal cancer cells in vivo, indicating that GE11-PEG-PEI may be a suitable gene vector for treating EGFR-overexpressing laryngeal cancer.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 93%

Peptide GE11–Polyethylene Glycol–Polyethylenimine for targeted gene delivery in laryngeal cancer

et al. 2015

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“…The selected peptides were YHWYGYTPQNVI (GE11) binding to EGFR 22 and two heptapeptides, MQLPLAT (M*) 23 and LSPPRYP (LS), 24 binding to FGFR1. To the best of our knowledge, none of these peptides have been tested previously for their ability to re-target a viral vector, though previous studies for GE11 have demonstrated the capacity of this peptide to target nanoparticles, 37 drugs, 38 nonviral gene therapy vectors, 39 , 40 and chemically modified Ad vectors 41 via the EGFR receptor, while the M* peptide has been utilized previously for targeted delivery of nonviral vectors. 23 , 42 …”

Section: Discussionmentioning

confidence: 99%

Incorporation of Peptides Targeting EGFR and FGFR1 into the Adenoviral Fiber Knob Domain and Their Evaluation as Targeted Cancer Therapies

et al. 2015

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Oncolytic virotherapies based on adenovirus 5 (Ad5) hold promise as adjunctive cancer therapies; however, their efficacy when delivered systemically is hampered by poor target cell specificity and preexisting anti-Ad5 immunity. Ovarian cancer represents a promising target for virotherapy, since the virus can be delivered locally into the peritoneal cavity. Both epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor 1 (FGFR1) are overexpressed in the majority of human tumors, including ovarian cancer. To generate adenoviral vectors with improved tumor specificity, we generated a panel of Ad5 vectors with altered tropism for EGFR and FGFR, rather than the natural Ad5 receptor, hCAR. We have included mutations within AB loop of the viral fiber knob (KO1 mutation) to preclude interaction with hCAR, combined with insertions in the HI loop to incorporate peptides that bind either EGFR (peptide YHWYGYTPQNVI, GE11) or FGFR1 (peptides MQLPLAT, M*, and LSPPRYP, LS). Viruses were produced to high titers, and the integrity of the fiber protein was validated by Western blotting. The KO1 mutation efficiently ablated hCAR interactions, and significantly increased transduction was observed in hCARlow/EGFRhigh cell lines using Ad5.GE11, while transduction levels using Ad5.M* or Ad5.LS were not increased. In the presence of physiological concentrations of human blood clotting factor X (hFX), significantly increased levels of transduction via the hFX-mediated pathway were observed in cell lines, but not in primary tumor cells derived from epithelial ovarian cancer (EOC) ascites samples. Ad5-mediated transduction of EOC cells was completely abolished by the presence of 2.5% serum from patients, while, surprisingly, incorporation of the GE11 peptide resulted in significant evasion of neutralization in the same samples. We thus speculate that incorporation of the YHWYGYTPQNVI dodecapeptide within the fiber knob domain may provide a novel means of circumventing preexisting Ad5 immunity that warrants further investigation.

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“…The most prominent peptide sequences are CMYIEALDKYAC [19, 20], YHWYGYTPQNVI (also known as “GE11”) [21–24] and LARLLT (also known as “D4”) [25–28]. For some highly cytotoxic drugs such as paclitaxel [23, 26] and doxorubicin [19, 20, 24], conjugates or targeted nanoformulations with these peptides were already reported to enhance the tumor specificity. Notably, such an approach has not been applied to platinum compounds so far.…”

Section: Introductionmentioning

confidence: 99%

EGFR-targeting peptide-coupled platinum(IV) complexes

et al. 2017

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The high mortality rate of lung cancer patients and the frequent occurrence of side effects during cancer therapy demonstrate the need for more selective and targeted drugs. An important and well-established target for lung cancer treatment is the occasionally mutated epidermal growth factor receptor (EGFR). As platinum(II) drugs are still the most important therapeutics against lung cancer, we synthesized in this study the first platinum(IV) complexes coupled to the EGFR-targeting peptide LARLLT (and the shuffled RTALLL as reference). Notably, HPLC–MS measurements revealed two different peaks with the same molecular mass, which turned out to be a transcyclization reaction in the linker between maleimide and the coupled cysteine moiety. With regard to the EGFR specificity, subsequent biological investigations (3-day viability, 14-day clonogenic assays and platinum uptake) on four different cell lines with different verified EGFR expression levels were performed. Unexpectedly, the results showed neither an enhanced activity nor an EGFR expression-dependent uptake of our new compounds. Consequently, fluorophore-coupled peptides were synthesized to re-evaluate the targeting ability of LARLLT itself. However, also with these molecules, flow cytometry measurements showed no correlation of drug uptake with the EGFR expression levels. Taken together, we successfully synthesized the first platinum(IV) complexes coupled to an EGFR-targeting peptide; however, the biological investigations revealed that LARLLT is not an appropriate peptide for enhancing the specific uptake of small-molecule drugs into EGFR-overexpressing cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1007/s00775-017-1450-7) contains supplementary material, which is available to authorized users.

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EGFR-targeted poly(ethylene glycol)-distearoylphosphatidylethanolamine micelle loaded with paclitaxel for laryngeal cancer: preparation, characterization andin vitroevaluation

Cited by 28 publications

References 46 publications

Peptide GE11–Polyethylene Glycol–Polyethylenimine for targeted gene delivery in laryngeal cancer

Peptide GE11–Polyethylene Glycol–Polyethylenimine for targeted gene delivery in laryngeal cancer

Incorporation of Peptides Targeting EGFR and FGFR1 into the Adenoviral Fiber Knob Domain and Their Evaluation as Targeted Cancer Therapies

EGFR-targeting peptide-coupled platinum(IV) complexes

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