Targeting the Hypoxic and Acidic Tumor Microenvironment with pH-Sensitive Peptides
Open Access
- 3 March 2021
- Vol. 10 (3), 541
- https://doi.org/10.3390/cells10030541
Abstract
The delivery of cancer therapeutics can be limited by pharmacological issues such as poor bioavailability and high toxicity to healthy tissue. pH-low insertion peptides (pHLIPs) represent a promising tool to overcome these limitations. pHLIPs allow for the selective delivery of agents to tumors on the basis of pH, taking advantage of the acidity of the hypoxic tumor microenvironment. This review article highlights the various applications in which pHLIPs have been utilized for targeting and treating diseases in hypoxic environments, including delivery of small molecule inhibitors, toxins, nucleic acid analogs, fluorescent dyes, and nanoparticles.Funding Information
- National Cancer Institute (5R35CA197574-04, 5F30CA221065-03)
- National Institute of General Medical Sciences (1T32GM136651-01)
This publication has 71 references indexed in Scilit:
- Family of pH (low) insertion peptides for tumor targetingProceedings of the National Academy of Sciences of the United States of America, 2013
- Antiproliferative Effect of pHLIP-AmanitinBiochemistry, 2013
- Small Molecules, Inhibitors of DNA-PK, Targeting DNA Repair, and BeyondFrontiers in Pharmacology, 2013
- pH (low) insertion peptide (pHLIP) targets ischemic myocardiumProceedings of the National Academy of Sciences of the United States of America, 2012
- Tuning a Polar Molecule for Selective Cytoplasmic Delivery by a pH (Low) Insertion PeptideBiochemistry, 2011
- Synthesis and Characterization of Conformationally Preorganized, (R)-Diethylene Glycol-Containing γ-Peptide Nucleic Acids with Superior Hybridization Properties and Water SolubilityThe Journal of Organic Chemistry, 2011
- Measuring Tumor Aggressiveness and Targeting Metastatic Lesions with Fluorescent pHLIPMolecular Imaging & Biology, 2010
- pH-(low)-insertion-peptide (pHLIP) translocation of membrane impermeable phalloidin toxin inhibits cancer cell proliferationProceedings of the National Academy of Sciences of the United States of America, 2010
- Mechanism and uses of a membrane peptide that targets tumors and other acidic tissues in vivoProceedings of the National Academy of Sciences of the United States of America, 2007
- Translocation of molecules into cells by pH-dependent insertion of a transmembrane helixProceedings of the National Academy of Sciences of the United States of America, 2006