Synthesis of angiogenesis-targeted peptide and hydrophobized polyethylene glycol conjugate

Maeda, Noriyuki; Takeuchi, Yoshito; Takada, Miki; Namba, Yukihiro; Oku, Naoto

doi:10.1016/j.bmcl.2003.11.073

Cited by 27 publications

(11 citation statements)

References 4 publications

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“…To investigate the potential of BiP as a target molecule for cancer antineovascular therapy, BiP‐targeted peptide‐modified liposomes were developed. Previously, it has been reported that DSPE‐PEG and peptides can be condensed with the DCC‐HOBt method 33. As indicated in Figure 4 a , the DSPE‐PEG conjugate of GWIFPWIQL‐peptides, which are shown to bind to BiP/GRP78,27 was synthesized.…”

Section: Resultsmentioning

confidence: 99%

Cancer antineovascular therapy with liposome drug delivery systems targeted to BiP/GRP78

Katanasaka

Ishii

Asai

et al. 2010

Intl Journal of Cancer

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Angiogenesis is crucial for tumor growth and hematogenous metastasis. Specifically expressed and functional protein molecules in angiogenic endothelial cells, especially on the plasma membrane, may be molecular targets for antiangiogenic drugs and drug delivery systems (DDS) in cancer therapy. To discover such target molecules, we performed subcellular proteome analysis of human umbilical vein endothelial cells (HUVECs) treated with or without vascular endothelial growth factor (VEGF) using 2‐dimensional difference in‐gel electrophoresis (2D‐DIGE) and matrix‐assisted laser desorption/ionization tandem time‐of‐flight mass spectrometry (MALDI‐TOF/TOF‐MS). Among the identified proteins, BiP/GRP78, a molecular chaperone, was highly expressed in the membrane/organelle fraction of HUVECs after VEGF treatment. The involvement of BiP in VEGF‐induced angiogenesis was examined by RNA interference. BiP knockdown significantly suppressed VEGF‐induced endothelial cell proliferation and VEGF‐induced phosphorylation of extracellular‐regulated kinase 1/2, phospholipase C‐γ, and VEGF receptor‐2 in HUVECs. Cell surface biotinylation analysis revealed that the cell surface expression of BiP was elevated in VEGF‐activated HUVECs. Aiming to apply BiP to a target molecule in liposomal DDS, we developed liposomes modified with the WIFPWIQL peptide, which has been shown to bind to BiP, and investigated its potential for cancer therapy. The WIFPWIQL‐modified liposomes (WIFPWIQL liposomes) were significantly taken up by VEGF‐activated HUVECs as compared to peptide‐unmodified liposomes. WIFPWIQL liposomes appeared to accumulate in tumor endothelial cells in vivo. WIFPWIQL liposomes containing doxorubicin significantly suppressed tumor growth and prolonged the survival of colon26 NL‐17 carcinoma cell‐bearing mice. In summary, BiP may regulate VEGF‐induced endothelial cell proliferation through VEGFR‐2‐mediated signaling and be an effective target molecule for cancer antineovascular therapy.

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Section: Resultsmentioning

confidence: 99%

Cancer antineovascular therapy with liposome drug delivery systems targeted to BiP/GRP78

Katanasaka

Ishii

Asai

et al. 2010

Intl Journal of Cancer

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“…A PET study allows us to analyze real time distribution change of liposomes under non-invasive conditions. Liposomes prelabeled with [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] F]FDG were injected into C26 NL-17-bearing mice, and PET analysis was performed. PET images (Fig.…”

Section: In Vivo Trafficking Of [2-mentioning

confidence: 99%

“…9,10) Therefore, we synthesized APRPG peptide attached to PEG termini of PEG-disteaoylphosphatidylethanolamine (PEG-DSPE) to prepare angiogenesis-targeted liposomes with long circulating characteristic. 11) We previously observed that ADM-encapsulated liposomes modified with APRPG-PEG caused more efficient tumor growth suppression than ADM-encapsulated liposomes modified with PEG alone in Colon 26 NL-17 carcinoma (C26 NL-17)-bearing mice, despite not so much different accumulation of both liposomes in the tumor. 12) To clarify the advantage of angiogenesis-targeted long-circulating liposomes, we examined the in vivo trafficking of APRPG-PEG-modified liposomes as well as non-modified or PEG-modified ones in tumor-baring mice with positron emission tomography (PET) in the present study: The method is able to determine the real time liposomal trafficking non-invasively.…”

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confidence: 95%

Enhancement of Anticancer Activity in Antineovascular Therapy Is Based on the Intratumoral Distribution of the Active Targeting Carrier for Anticancer Drugs

Maeda

Miyazawa

Shimizu

et al. 2006

Biological & Pharmaceutical Bulletin

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“…It has been shown that disulfide-stabilized peptides containing an Arg-Gly-Asp (RGD)-motif can interact with high affinity and avidity to alpha v-integrins [15][16][17]. Other peptides that have been shown to specifically interact with angiogenic endothelial cells are peptides containing an NGR-motif (binding to aminopeptidase N [18]), ATWLPPR (binding to VEGFR2 [19][20][21]), and APRPG (binding an unknown target [22,23]). …”

Section: Targeting Angiogenesismentioning

confidence: 99%

Transporting silence: Design of carriers for siRNA to angiogenic endothelium

Schiffelers

Mixson

Ansari³

et al. 2005

Journal of Controlled Release

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The recently developed siRNA oligonucleotides are an attractive alternative to antisense as a therapeutic modality because of their robust, gene selective silencing of drug target protein expression. To achieve therapeutic success, however, several hurdles must be overcome including rapid clearance, nuclease degradation, and inefficient intracellular localization. In this presentation, we discuss design strategies for development of self-assembling nanoscale carriers for neovasculature targeted delivery of siRNA inhibiting tumor or ocular angiogenesis. D

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Synthesis of angiogenesis-targeted peptide and hydrophobized polyethylene glycol conjugate

Cited by 27 publications

References 4 publications

Cancer antineovascular therapy with liposome drug delivery systems targeted to BiP/GRP78

Cancer antineovascular therapy with liposome drug delivery systems targeted to BiP/GRP78

Enhancement of Anticancer Activity in Antineovascular Therapy Is Based on the Intratumoral Distribution of the Active Targeting Carrier for Anticancer Drugs

Transporting silence: Design of carriers for siRNA to angiogenic endothelium

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