Abstract | 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: 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 | Ghazal Hariri, Heping Yan, Hailun Wang, Zhaozhong Han, Dennis E Hallahan |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 16
Issue 20
Pg. 4968-77
(Oct 15 2010)
ISSN: 1557-3265 [Electronic] United States |
PMID | 20802016
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | ©2010 AACR. |
Chemical References |
- 130-nm albumin-bound paclitaxel
- Albumins
- Peptides
- Paclitaxel
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Topics |
- 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
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