Document Detail


Radiation-guided drug delivery to mouse models of lung cancer.
MedLine Citation:
PMID:  20802016     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ghazal Hariri; Heping Yan; Hailun Wang; Zhaozhong Han; Dennis E Hallahan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-27
Journal Detail:
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:
Created Date:  2010-10-15     Completed Date:  2010-12-14     Revised Date:  2013-02-13    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4968-77     Citation Subset:  IM    
Copyright Information:
©2010 AACR.
Affiliation:
Department of Radiation Oncology, Vanderbilt University, Nashville, Tennessee, USA.
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MeSH Terms
Descriptor/Qualifier:
Albumins / 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:
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:
0/130-nm albumin-bound paclitaxel; 0/Albumins; 0/Peptides; 33069-62-4/Paclitaxel

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