Applications of pHLIP Technology for Cancer Imaging and Therapy

pHLIP®s target cancer cells in primary tumors as well as metastases based on the acidic environment that is universal to tumor tissues. Acidity-based targeting is not diminished by the phenomena that blunt the efficacy of other biomarker-based targeting methods. pHLIPs exist as monomers and remain anchored across the membrane, leaving it intact, which distinguishes them from pore-forming and cell-penetrating peptides. A growing family of pHLIP variants gives choices for the delivery of various cargoes, including imaging agents for nuclear diagnostic imaging and fluorescence guided surgery, cell-permeable and impermeable therapeutic agents for intracellular delivery, and different types of nanoparticles. pHLIPs show promise for many medical applications, and the clinical translation of several pHLIP conjugates is currently underway. Acidity is a biomarker of cancer that is not subject to the blunting clonal selection effects that reduce the efficacy of other biomarker technologies, such as antibody targeting. The pH (low) insertion peptides (pHLIP®s) provide new opportunities for targeting acidic tissues. Through the physical mechanism of membrane-associated folding, pHLIPs are triggered by the acidic microenvironment to insert and span the membranes of tumor cells. The pHLIP platform can be applied to imaging acidic tissues, delivering cell-permeable and impermeable molecules to the cytoplasm, and promoting the cellular uptake of nanoparticles. Since acidosis is a hallmark of tumor development, progression, and aggressiveness, the pHLIP technology may prove useful in targeting cancer cells and metastases for tumor diagnosis, imaging, and therapy. Acidity is a biomarker of cancer that is not subject to the blunting clonal selection effects that reduce the efficacy of other biomarker technologies, such as antibody targeting. The pH (low) insertion peptides (pHLIP®s) provide new opportunities for targeting acidic tissues. Through the physical mechanism of membrane-associated folding, pHLIPs are triggered by the acidic microenvironment to insert and span the membranes of tumor cells. The pHLIP platform can be applied to imaging acidic tissues, delivering cell-permeable and impermeable molecules to the cytoplasm, and promoting the cellular uptake of nanoparticles. Since acidosis is a hallmark of tumor development, progression, and aggressiveness, the pHLIP technology may prove useful in targeting cancer cells and metastases for tumor diagnosis, imaging, and therapy. peptides with both hydrophobic and hydrophilic regions that insert and assemble to form pores in the cellular membrane. a peptide, typically with a strong positive charge, that binds to the phospholipids of the cell membrane and is taken up by the cell. a molecule that exhibits properties similar to those of established drugs; for example, per Lipinski's Rule of Five: no more than five hydrogen bond donors, no more than ten hydrogen bond acceptors, molecular weight <500 Da, and an octanol-water partition coefficient log P ≤5. filaments that are part of the cell cytoskeleton and contribute to structural stability and cell movement. a US Food and Drug Administration (FDA)-approved fluorescent dye used to mark blood vessels in angiography and perfusion diagnostics, but does not target the tumor itself. small molecules of RNA that have a functional role in gene expression by blocking messenger RNA translation. amino acids that are not encoded in the human genome. the ability of molecules to cross cell membranes on their own. targeting methods that rely on naturally occurring biological characteristics, such as non-intact tumor vasculature, to induce the localization of cargo within a tumor. an artificial DNA- or RNA-like molecule with a peptide backbone that forms a sequence-specific base-paired complex with DNA or RNA. pHLIP is a registered trademark. the condition that exists after surgical resection when the surgery was not successful in removing all cancerous tissue. a member of the large family of G-protein-coupled receptors that has a functional role in blood coagulation. a key enzyme that catalyzes transcription. a fluorescent dye with two pH-dependent emission peaks, making it possible to use SNARF to measure pH through spectrography or ratiometric imaging. a protein that is exposed to the blood upon tissue damage, triggering blood clot formation. the formation by a polypeptide of a helix that spans the lipid bilayer of a cellular membrane. any breast cancer that does not express the estrogen receptor, progesterone receptor, and epidermal growth factor receptor 2 (HER2/neu). Triple-negative breast cancer is difficult to treat due to the reliance of typical chemotherapies on the expression of one or more of these receptors. a family of proteins that polymerize into microtubules, which are part of the cytoskeleton and contribute to structural stability, cytoplasmic transport, cell movement, and cell division. the spread of cancer cells (metastasis) from the primary tumor site to adjacent tissue or blood. Applications of pHLIP Technology for Cancer Imaging and Therapy: (Trends in Biotechnology , 653–664, 2017)Wyatt et al.Trends in BiotechnologyNovember 30, 2017In BriefThe following declaration of interests was inadvertently omitted from the published article: Full-Text PDF