Abstract |
Solid tumors often display metabolic abnormalities that consistently produce low pH in the extracellular space of poorly perfused tissue. These acidic regions may provide a mechanism for drug targeting. Peptides have been designed in such a manner that they exist in an anionic hydrophilic form at the pH of normal tissues, but then undergo a sharp transition to a non-ionic lipophilic form at reduced pH. Peptides were labeled with fluorescein or technetium-99m (99mTc) and evaluated in vitro and in two murine models of cancer. Our studies suggest that PAP-1, an 18 amino acid pH activated peptide with a pH of transition between hydrophilic and lipophilic forms (pT) of 6.4, will deliver fluorescein and 99mTc to tumors. Activation of PAP-1 by low pH and penetration into the plasma membrane of cells and tumors were confirmed using flow cytometry, fluorescence microscopy, and gamma scintigraphy. These results support our central hypothesis that PAP-1 may enable the selective delivery of macromolecules to tumors. This technology has potential for exploiting a common property of tumors to achieve highly specific medical intervention.
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Authors | John E Mata, Leslie A Dyal, Margorie E Slauson, James E Summerton, Christiane Loehr, Arhie Reid Tyson, Rosita Rodriguez-Proteau, Scott B Gustafson |
Journal | Nanomedicine : nanotechnology, biology, and medicine
(Nanomedicine)
Vol. 3
Issue 4
Pg. 297-305
(Dec 2007)
ISSN: 1549-9642 [Electronic] United States |
PMID | 17900997
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Pancreatitis-Associated Proteins
- Peptides
- REG3A protein, human
- Radiopharmaceuticals
- Technetium
|
Topics |
- Animals
- Cell Line, Tumor
- Hydrogen-Ion Concentration
- Image Enhancement
(methods)
- Lung Neoplasms
(diagnostic imaging, metabolism)
- Mammary Neoplasms, Animal
(diagnostic imaging, metabolism)
- Metabolic Clearance Rate
- Mice
- Pancreatitis-Associated Proteins
- Peptides
(pharmacokinetics)
- Protein Binding
- Radionuclide Imaging
- Radiopharmaceuticals
(pharmacokinetics)
- Technetium
(pharmacokinetics)
- Tissue Distribution
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