| Radiation-guided drug delivery to mouse models of lung cancer. | |
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MedLine Citation:
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PMID: 20802016 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: The purpose of this study was to achieve improved cancer-specific delivery and bioavailability of radiation-sensitizing chemotherapy using radiation-guided drug delivery. EXPERIMENTAL DESIGN: Phage display technology was used to isolate a recombinant peptide (HVGGSSV) that binds to a radiation-inducible receptor in irradiated tumors. This peptide was used to target nab-paclitaxel to irradiated tumors, achieving tumor-specificity and enhanced bioavailability of paclitaxel. RESULTS: Optical imaging studies showed that HVGGSSV-guided nab-paclitaxel selectively targeted irradiated tumors and showed 1.48 ± 1.66 photons/s/cm(2)/sr greater radiance compared with SGVSGHV-nab-paclitaxel, and 1.49 ± 1.36 photons/s/cm(2)/sr greater than nab-paclitaxel alone (P < 0.05). Biodistribution studies showed >5-fold increase in paclitaxel levels within irradiated tumors in HVGGSSV-nab-paclitaxel-treated groups as compared with either nab-paclitaxel or SGVSGHV-nab-paclitaxel at 72 hours. Both Lewis lung carcinoma and H460 lung carcinoma murine models showed significant tumor growth delay for HVGGSSV-nab-paclitaxel as compared with nab-paclitaxel, SGVSGHV-nab-paclitaxel,and saline controls. HVGGSSV-nab-paclitaxel treatment induced a significantly greater loss in vasculature in irradiated tumors compared with unirradiated tumors, nab-paclitaxel, SGVSGHV-nab-paclitaxel, and untreated controls. CONCLUSIONS: HVGGSSV-nab-paclitaxel was found to bind specifically to the tax-interacting protein-1 (TIP-1) receptor expressed in irradiated tumors, enhance bioavailability of paclitaxel, and significantly increase tumor growth delay as compared with controls in mouse models of lung cancer. Here we show that targeting nab-paclitaxel to radiation-inducible TIP-1 results in increased tumor-specific drug delivery and enhanced biological efficacy in the treatment of cancer. |
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Authors:
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Ghazal Hariri; Heping Yan; Hailun Wang; Zhaozhong Han; Dennis E Hallahan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-08-27 |
Journal Detail:
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Title: Clinical cancer research : an official journal of the American Association for Cancer Research Volume: 16 ISSN: 1078-0432 ISO Abbreviation: Clin. Cancer Res. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-15 Completed Date: 2010-12-14 Revised Date: 2013-02-13 |
Medline Journal Info:
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Nlm Unique ID: 9502500 Medline TA: Clin Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 4968-77 Citation Subset: IM |
Copyright Information:
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©2010 AACR. |
Affiliation:
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Department of Radiation Oncology, Vanderbilt University, Nashville, Tennessee, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Albumins
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administration & dosage*,
chemistry,
pharmacokinetics Amino Acid Sequence Animals Biological Availability Carcinoma, Large Cell / drug therapy*, metabolism, radiotherapy Carcinoma, Lewis Lung / drug therapy*, metabolism, radiotherapy Cell Line, Tumor Disease Models, Animal Drug Delivery Systems / methods* Guinea Pigs Humans Lung Neoplasms / drug therapy*, metabolism, radiotherapy Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Nude Molecular Sequence Data Paclitaxel / administration & dosage*, chemistry, pharmacokinetics Peptides / administration & dosage*, chemistry, pharmacokinetics Rabbits Tissue Distribution Xenograft Model Antitumor Assays |
| Grant Support | |
ID/Acronym/Agency:
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5R01-CA112385-05/CA/NCI NIH HHS; 5R01-CA125757-03/CA/NCI NIH HHS; P50-CA128323/CA/NCI NIH HHS; R01 CA125757-06/CA/NCI NIH HHS; R01 CA140220/CA/NCI NIH HHS; R21-CA128456-02/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/130-nm albumin-bound paclitaxel; 0/Albumins; 0/Peptides; 33069-62-4/Paclitaxel |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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