A novel small peptide as a targeting ligand for receptor tyrosine kinase Tie2

Wu, Xianghua; Zhao, Ruijiao; Li, Zonghai; Yao, Ming; Wang, Huamao; Han, Junsong; Qu, Shumin; Chen, Xianlian; Qian, Lianfang; Sun, Ye; Xu, Yuhong; Gu, Jianren

doi:10.1016/j.bbrc.2004.01.157

Cited by 12 publications

(11 citation statements)

References 24 publications

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“…Screening of phage display libraries, 8,23 CAD, 10 hydropathic complementarity, 24 hydropathic analysis, and comparative sequence/structure analysis 7 have been used to design small peptide ligands. In this study, we demonstrated different methods of screening for small molecule peptide ligands.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, small peptides are pursued as targeting moieties because of their small size, low immunogenicity, and their ability to be incorporated into certain delivery vectors. [7][8][9][10][11][12] The epidermal growth factor receptor (EGFR) is a transmembrane protein on the cell surface that is overexpressed in a wide variety of human cancers. EGFR is an effective tumor-specific target because of its significant functions in tumor cell growth, differentiation, and migration.…”

Section: Introductionmentioning

confidence: 99%

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A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro

Han¹,

Yue²,

Tai³

et al. 2013

IJN

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Abstract:The epidermal growth factor receptor (EGFR) serves an important function in the proliferation of tumors in humans and is an effective target for the treatment of cancer. In this paper, we studied the targeting characteristics of small peptides (AEYLR, EYINQ, and PDYQQD) that were derived from three major autophosphorylation sites of the EGFR C-terminus domain in vitro. These small peptides were labeled with fluorescein isothiocyanate (FITC) and used the peptide LARLLT as a positive control, which bound to putative EGFR selected from a virtual peptide library by computer-aided design, and the independent peptide RALEL as a negative control. Analyses with flow cytometry and an internalization assay using NCI-H1299 and K562 with high EGFR and no EGFR expression, respectively, indicated that FITC-AEYLR had high EGFR targeting activity. Biotin-AEYLR that was specifically bound to human EGFR proteins demonstrated a high affinity for human non-small-cell lung tumors. We found that AEYLR peptide-conjugated, nanostructured lipid carriers enhanced specific cellular uptake in vitro during a process that was apparently mediated by tumor cells with high-expression EGFR. Analysis of the MTT assay indicated that the AEYLR peptide did not significantly stimulate or inhibit the growth activity of the cells. These findings suggest that, when mediated by EGFR, AEYLR may be a potentially safe and efficient delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro

Han¹,

Yue²,

Tai³

et al. 2013

IJN

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“…Targeting moieties have included many peptides, carbohydrates, monoclonal antibodies and natural ligands such as transferrin [Cotten M, et al, 1990;Maruta F 2002;Trubetskoy et al 1992;Wadhwa MS, et al, 1995;Wu et al 2004]. In most cases, the targeting moieties are covalently attached to the polycation prior to mixing with DNA for particle formation.…”

Section: (B) Targeted Gene Deliverymentioning

confidence: 99%

Synthetic Peptides As Non-Viral DNA Vectors

Fabre¹,

Collins²

2006

CGT

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The use of multiple peptide motifs to provide effective gene delivery holds great promise as an elegant, non-immunogenic approach to gene therapy. The molecular understanding of cell and viral biology provides a strong foundation on which to pursue this objective. Synthetic peptides containing multiple lysines and/or arginines (occasionally ornithines) provide natural polycations for multivalent electrostatic binding of DNA, and for DNA compaction into particles suitable for gene delivery. These cationic peptides can incorporate additional functional motifs (e.g. for translocating DNA into the nucleus) and they can be linked by disulphide bonds to produce high molecular reducible polycations with superior properties for gene therapy. Many factors influence the size, surface charge and stability of peptide/DNA particles. For in vivo use, uncharged particles resistant to disruption by salt and protein, and targeted to tissue-specific membrane molecules, will be required. Entry into the cell is via one of the endocytic pathways, depending on particle size and (in principle) the target cell surface molecule. Peptide motifs for endocytic escape are based mainly on the anionic fusogenic peptide of influenza virus haemagglutinin and on histidine-rich peptides (where the buffering properties of the imidazole group cause osmotic swelling and probably rupture of endocytic vesicles). Once in the cytosol, translocation of DNA plasmids across the nuclear pore complex into the nucleus is a crucial step, because most target cells for gene therapy are either non-dividing or slowly dividing. Nuclear translocation can be achieved by classical nuclear localising motifs, or more simply by (Lys)16 and other cationic peptides.

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“…This surface protein was found to be a marker of tumor microvasculature [184] correlating with the grade of vascularization and is also a prognostic marker for malignancy [185]. Wu et al identified a peptide sequence GA3 binding to the Tie2 receptor with high affinity and specificity in vitro as well as in vivo [186].…”

Section: Tie2mentioning

confidence: 99%

Specific Targets in Tumor Tissue for the Delivery of Therapeutic Genes

Günther¹,

Wagner²,

Ogris

2005

CMCACA

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Gene therapy is part of a growing field in molecular medicine, which will gain importance in the treatment of human diseases. Until now, almost two thirds of all clinical trials performed in gene therapy are directed against Cancer As solid tumors exceeding a certain size rely on blood supply, the administration of particulate gene delivery vectors via the bloodstream is a promising concept. Tumor cells and the tumor vasculature both offer specific molecular targets, which can be utilized for the site directed delivery of therapeutic genes. Passive targeting of macromolecular drugs including gene delivery vectors to tumors can be achieved by the so called enhanced permeability and retention (EPR) effect. The specificity can be markedly enhanced when tumor targeting ligands are used. Viral vectors, which usually do not have a natural tropism for tumor tissue, were generated to carry tumor targeting molecules on their surface. Synthetic gene delivery vectors, based on cationic lipids or cationic polymers were biochemically modified to incorporate ligands specific for tumor cells or tumor vasculature. For systemic application, these delivery systems have to fulfill certain conditions. The delivery vector should not induce any immunogenic and inflammatory responses. Several studies were conducted to reduce the immunogenicity of viral vectors; surface modification of non-viral gene delivery systems reduced their non-specific interaction with blood components. On the genetic level, tumor specific promoters add additional layers of specificity restricting the transgene expression to the tumor tissue. This review will cover the systemic application of particulate gene transfer vectors targeted to tumors and will give an overview of therapeutic concepts for cancer gene therapy.

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A novel small peptide as a targeting ligand for receptor tyrosine kinase Tie2

Cited by 12 publications

References 24 publications

A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro

A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro

Synthetic Peptides As Non-Viral DNA Vectors

Specific Targets in Tumor Tissue for the Delivery of Therapeutic Genes

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