Open AccessPharmacokinetic modeling reveals parameters that govern tumor targeting and delivery by a pH-Low Insertion Peptide (pHLIP)
Author(s) -
Alexander A. Svoronos,
Donald M. Engelman
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2016605118
Subject(s) - peptide , drug delivery , extracellular , chemistry , cell , biochemistry , biophysics , microbiology and biotechnology , biology , organic chemistry
Significance Tumors exhibit an acidic extracellular microenvironment that is accentuated at cell surfaces. As a result, they can be targeted by a pH-Low Insertion Peptide (pHLIP), an acid-triggered tumor-targeting peptide that can also serve as a vehicle for drug delivery. In this work, we use a pharmacokinetic modeling approach to deepen our understanding of the mechanisms and factors that influence pHLIP tumor targeting and delivery, and also identify factors that do not. In so doing, we predict pHLIP phenotypes with significantly enhanced capabilities. The model may therefore be useful for guiding the future development of pHLIP variants.