pH (Low) Insertion Peptide Targets 4T1 Mammary Tumors

Malignant tumors exhibit elevated uptake and use of glucose, as well as metabolite buildup and hypoxia due to inadequate blood supply, leading to tumor acidosis. The extracellular acidity is linked to tumor progression. The most effective pH-sensitive tumor targeting agents should sense pH at the surface of cancer cells, where it is expected to be the lowest. pHLIPs (R) (pH (Low) Insertion Peptides) belong to the class of pH-sensitive agents capable of delivering imaging and/or therapeutic agents to cancer cells within tumors. Here, we investigated targeting of highly metastatic 4T1 mammary tumors in BALB/c mice with three Alexa546 labeled pHLIP variants including well-characterized WT-pHLIP and, recently introduced, Var3- and Var7-pHLIPs.