Nanoprobe Directed Tumor Imaging Using pH Activated Peptides as Contrast Agent Carriers.

摘要

We characterized a class of modified peptides designed to activate in the extracellular space of tumors in which pH is below 7.0 in cell culture and in tumor bearing mice. These 'molecular engines' change shape in a low pH environment, become lipophilic, and embed into the plasma membrane. Our studies suggest that a molecular engine with a pT of 6.8-6.9 will deliver an 8-carboxyfluoroscein ligand to the surface of tumor cells in C57blk-J6 mice bearing subcutaneously transplanted Lewis lung cell-derived tumors following an iv injection of 27 nmoles (0.1 mg) peptide with FITC-labeled ligand. These observations were confirmed by flow cytometric analysis. Proof of principle for their diagnostic utility of this technology was obtained by injection of a 99mTc labeled peptide followed by gamma scintigraphy. This technology has tremendous potential for highly specific medical intervention at the molecular scale.