期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 3, 期 4, 页码 297-305出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2007.08.001
关键词
drug delivery; tumor imaging; peptide delivery; nanotechnology; cancer
资金
- NCRR NIH HHS [1S10RR107903-01] Funding Source: Medline
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 technicium-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. Published by Elsevier Inc.
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