Abstract
The pH-Low Insertion Peptide (pHLIP) has emerged as an important tool for targeting cancer cells. It has been assumed that its targeting mechanism depends solely on the mild acidic environment surrounding tumors. Here, we examine the role of the two predominant extracellular divalent cations, Ca2+ and Mg2+, on pHLIP's cellular targeting, insertion, and drug delivery. Using a combination of cellular and spectroscopic techniques we demonstrate that physiologically-relevant concentrations of either cation drastically promote the interaction and insertion of pHLIP.
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