Peptide-targeted PEG-liposomes in anti-angiogenic therapy

Janssen, Adrienne P.C.A.

doi:10.1016/s0378-5173(02)00682-8

Cited by 72 publications

(29 citation statements)

References 7 publications

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“…The ATWLPPR peptide has already been used in several in vitro and in vivo studies (Janssen et al, 2003;Rodrigues et al, 2003;Perret et al, 2004;Renno et al, 2004), but, to the best of our knowledge, none has reported on its instability. The present study draws attention to this potential problem with peptides, especially in the case of targeting strategies, and provides useful information for the choice of the DLI for in vivo assessments of photodynamic activity and for the future design of more stable molecules.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Profile of a Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1: An in Vivo and in Vitro Study

Tirand¹,

Thomas²,

Dodeller³

et al. 2007

Drug Metab Dispos

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ABSTRACT:Because angiogenic endothelial cells of the tumor vasculature represent an interesting target to potentiate the antivascular effect of photodynamic therapy, we recently described the conjugation of a photosensitizer [5-(4-carboxyphenyl)-10,15,20-triphenylchlorin (TPC)], via a spacer [6-aminohexanoic acid (Ahx)], to a vascular endothelial growth factor receptor-specific heptapeptide [H-AlaThr-Trp-Leu-Pro-Pro-Arg-OH (ATWLPPR)] and showed that TPCAhx-ATWLPPR binds to neuropilin-1. Because peptides often display low stability in biological fluids, we examined the in vivo and in vitro stability of this conjugate by high-performance liquid chromatography and matrix-assisted laser desorption ionization/time of flight mass spectrometry. TPC-Ahx-ATWLPPR was stable in vitro in human and mouse plasma for at least 24 h at 37°C but, following i.v. injection in glioma-bearing nude mice, was degraded in vivo to various rates, depending on the organ considered. TPCAhx-A was identified as the main metabolic product, and biodistribution studies suggested that its appearance in plasma mainly resulted from the degradation of the peptidic moiety into organs of the reticuloendothelial system. According to in vitro cell culture experiments, TPC-Ahx-ATWLPPR was also significantly degraded after incorporation in human umbilical vein endothelial cells (HUVEC), mainly into TPC-Ahx-A and to a lesser extent into TPCAhx-AT and TPC-Ahx-ATWLPP. TPC-Ahx-ATWLPPR mostly localized into lysosomes, and when HUVEC were treated with the lysosomal enzymes' inhibitor ammonium chloride, this resulted in a significant decrease of the peptide degradation. This study provides essential information for the choice of the time of activation of the photosensitizer (drug-light interval) not to be exceeded and for the future design of more stable molecules.

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Section: Discussionmentioning

confidence: 99%

Metabolic Profile of a Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1: An in Vivo and in Vitro Study

Tirand¹,

Thomas²,

Dodeller³

et al. 2007

Drug Metab Dispos

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“…Scattered sites of leakage of phage particles resemble the patchy distribution of extravasated antibodies observed in the present study. Further evidence of binding to luminal integrins comes from studies of RGD-targeted 100-nm liposomes used to deliver doxorubicin to tumors in preclinical models (26,27). The Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Rapid Access of Antibodies to α5β1 Integrin Overexpressed on the Luminal Surface of Tumor Blood Vessels

Magnussen

Kasman²,

Norberg³

et al. 2005

Cancer Research

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Integrin A 5 B 1 is overexpressed on endothelial cells of tumor vessels and is uniformly and rapidly accessible to antibodies in the bloodstream. Here, we determined whether antibodies rapidly gain access to integrin overexpressed on the abluminal (basolateral) surface of endothelial cells through vascular leakiness or whether the rapid accessibility results instead because the integrin is overexpressed on the luminal (apical) surface of endothelial cells due to loss of cell polarity. Using tumors in RIP-Tag2 transgenic mice as a model, we first compared the binding pattern of intravascular anti-A 5 B 1 integrin antibody with the leakage pattern of nonspecific IgG. The distributions did not match: anti-A 5 B 1 integrin antibody uniformly labeled the tumor vasculature, but IgG was located in patchy sites of leakage. We next injected an antibody to fibrinogen/fibrin, which resulted in patchy labeling of tumors that matched the leakage of IgG and the overall distribution of fibrin in tumors. Similarly, injected antibodies to the basement membrane protein fibronectin, a ligand of A 5 B 1 integrin, or type IV collagen produced patchy sites of leakage instead of uniform labeling of vascular basement membrane. Differences in the kinetics of labeling, which for A 5 B 1 integrin antibody was near maximal by 10 minutes but for the other antibodies gradually increased over 6 hours, indicated differences in accessibility of their respective targets. Isosurface rendering of confocal microscopic images was consistent with antibody binding to A 5 B 1 integrin on the luminal surface of endothelial cells. Together, these findings indicate that the rapid accessibility of A 5 B 1 integrin in RIP-Tag2 tumors results from overexpression of the integrin on the luminal surface of tumor vessels. (Cancer Res 2005; 65(7): 2712-21)

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“…There are several reasons why viruses are an excellent choice in this regard. First, rigid viral capsids provide natural molecular scaffolds that allow precise attachments for building nanostructures, with control over orientation and spacing that is not attainable using other materials, such as dendrimers or liposomes (14,26,29,31,46). Second, virus capsids use highly repeated structural motifs allowing for the polyvalent display of peptides (11), polysaccharides (22,48), nucleic acids (54), or other synthetic structures (43).…”

mentioning

confidence: 99%

Interaction between a 54-Kilodalton Mammalian Cell Surface Protein and Cowpea Mosaic Virus

Koudelka

Rae

Gonzalez

et al. 2007

J Virol

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Cowpea mosaic virus (CPMV), a plant virus that is a member of the picornavirus superfamily, is increasingly being used for nanotechnology applications, including material science, vascular imaging, vaccine development, and targeted drug delivery. For these applications, it is critical to understand the in vivo interactions of CPMV within the mammalian system. Although the bioavailability of CPMV in the mouse has been demonstrated, the specific interactions between CPMV and mammalian cells need to be characterized further. Here we demonstrate that although the host range for replication of CPMV is confined to plants, mammalian cells nevertheless bind and internalize CPMV in significant amounts. This binding is mediated by a conserved 54-kDa protein found on the plasma membranes of both human and murine cell lines. Studies using a deficient cell line, deglycosidases, and glycosylation inhibitors showed that the CPMV binding protein (CPMV-BP) is not glycosylated. A possible 47-kDa isoform of the CPMV-BP was also detected in the organelle and nuclear subcellular fraction prepared from murine fibroblasts. Further characterization of CPMV-BP is important to understand how CPMV is trafficked through the mammalian system and may shed light on how picornaviruses may have evolved between plant and animal hosts.In the past several years, aside from understanding the natural life cycles of viruses as obligate intracellular pathogens, the power of viruses as tools for material applications has begun to be harnessed. There are several reasons why viruses are an excellent choice in this regard. First, rigid viral capsids provide natural molecular scaffolds that allow precise attachments for building nanostructures, with control over orientation and spacing that is not attainable using other materials, such as dendrimers or liposomes (14,26,29,31,46). Second, virus capsids use highly repeated structural motifs allowing for the polyvalent display of peptides (11), polysaccharides (22, 48), nucleic acids (54), or other synthetic structures (43). Selfassembly of virus capsids also ensures a lack of morphological polydispersity in the capsid size and shape, which is difficult to accomplish using synthetic materials (35,36). Third, viral genomes are generally easy to manipulate, allowing the generation of mutants that can allow specific tailoring of the particle surface (12,13,60,61). Fourth, procedures for inexpensive, efficient amplification of many such structures, e.g., plant viruses, virus-like particles, and bacteriophages, are already well defined (24,25,41,49,67).Plant viruses are especially attractive for development in material science, nanotechnology, and vaccine applications because of their ease of production and purification. In particular, cowpea mosaic virus (CPMV) has been studied increasingly as a material for these purposes. CPMV is the type member of the genus Comovirus, which is part of the Picornaviridae superfamily spanning the plant and animal kingdoms and including Poliovirus and Rhinovirus. CPMV has a singl...

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Peptide-targeted PEG-liposomes in anti-angiogenic therapy

Cited by 72 publications

References 7 publications

Metabolic Profile of a Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1: An in Vivo and in Vitro Study

Metabolic Profile of a Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1: An in Vivo and in Vitro Study

Rapid Access of Antibodies to α5β1 Integrin Overexpressed on the Luminal Surface of Tumor Blood Vessels

Interaction between a 54-Kilodalton Mammalian Cell Surface Protein and Cowpea Mosaic Virus

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