{"id":417,"date":"2022-04-13T16:22:37","date_gmt":"2022-04-13T16:22:37","guid":{"rendered":"http:\/\/physics.uri.edu\/biophysics\/?page_id=417"},"modified":"2022-04-20T20:27:18","modified_gmt":"2022-04-20T20:27:18","slug":"phlip-technology","status":"publish","type":"page","link":"https:\/\/physics.uri.edu\/biophysics\/phlip-technology\/","title":{"rendered":"pHLIP Technology"},"content":{"rendered":"<section class=\"cl-wrapper cl-menu-wrapper\"><div id=\"\" class=\"cl-menu  \" data-name=\"research\" data-show-title=\"0\"><ul id=\"menu-research\" class=\"cl-menu-list cl-menu-list-no-js\"><li id=\"menu-item-719\" class=\"menu-item menu-item-type-post_type menu-item-object-page menu-item-719\"><a href=\"https:\/\/physics.uri.edu\/biophysics\/molecular-mechanism-of-membrane-associated-folding-and-unfolding\/\">Membrane Folding<\/a><\/li>\n<li id=\"menu-item-717\" class=\"menu-item menu-item-type-post_type menu-item-object-page menu-item-717\"><a href=\"https:\/\/physics.uri.edu\/biophysics\/phlip-technology\/\">pHLIP Technology<\/a><\/li>\n<li id=\"menu-item-718\" class=\"menu-item menu-item-type-post_type menu-item-object-page menu-item-718\"><a href=\"https:\/\/physics.uri.edu\/biophysics\/phlic-technology\/\">pHLIC Technology<\/a><\/li>\n<li id=\"menu-item-720\" class=\"menu-item menu-item-type-post_type menu-item-object-page menu-item-720\"><a href=\"https:\/\/physics.uri.edu\/biophysics\/protein-fluorescence\/\">Protein Fluorescence<\/a><\/li>\n<\/ul><\/div><\/section>\n\n\n\n<h1 class=\"wp-block-heading\">pHLIP Technology<\/h1>\n\n\n\n<p class=\"has-normal-font-size\"><strong>pHLIP<sup>\u00ae<\/sup><\/strong> <strong>technology <\/strong>constitutes family of pH-Low Insertion Peptides, a novel class of pH-sensitive delivery agents, which selectively target and deliver diagnostic and therapeutic molecules to tumors. pHLIPs are linear peptides that sense cell-surface pH. They are moderately hydrophobic 25-35 aa peptides containing protonatable carboxyl groups. At&nbsp; normal&nbsp; pH, pHLIP&nbsp;peptides exist&nbsp; in&nbsp; unstructured,&nbsp; coil conformations&nbsp; in solution and&nbsp; at&nbsp; the&nbsp; surfaces&nbsp; of the membranes of normal cells. At the low surface pH of metabolically active cells, the negatively-charged residues become protonated. As a result, the hydrophobicity of the peptide increases, and triggers spontaneous membrane insertion, which is accompanied by the folding of the peptide to form a stable transmembrane&nbsp; helix. One terminus stays exposed to extracellular space and another terminus goes across membrane into cytoplasm.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"alignleft size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-2-copy-1024x431.jpg\" alt=\"\" class=\"wp-image-517\" width=\"768\" height=\"323\" srcset=\"https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-2-copy-1024x431.jpg 1024w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-2-copy-300x126.jpg 300w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-2-copy-768x323.jpg 768w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-2-copy-364x153.jpg 364w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-2-copy-500x210.jpg 500w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-2-copy-1000x421.jpg 1000w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-2-copy-1280x539.jpg 1280w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-2-copy.jpg 1478w\" sizes=\"auto, (max-width: 768px) 100vw, 768px\" \/><figcaption>Image is from Wyatt et al., <em>Trends Biotechnol.<\/em> 2017<\/figcaption><\/figure><\/div>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p class=\"has-normal-font-size\"><strong><strong>pHLIP<sup>\u00ae<\/sup> Technology for Extracellular Delivery<\/strong><\/strong>:  pHLIP peptides can be used for&nbsp; extracellular targeted delivery of imaging and therapeutic payloads (small molecules and proteins)&nbsp; for decoration of cancer cells in tumors.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"alignleft size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-1.jpg\" alt=\"\" class=\"wp-image-514\" width=\"743\" height=\"349\" srcset=\"https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-1.jpg 990w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-1-300x141.jpg 300w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-1-768x361.jpg 768w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-1-364x171.jpg 364w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-1-500x235.jpg 500w\" sizes=\"auto, (max-width: 743px) 100vw, 743px\" \/><figcaption>Image is from Reshetnyak et al., <em>Front Bioeng Biotechnol.<\/em> 2020<\/figcaption><\/figure><\/div>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p class=\"has-normal-font-size\"><strong><strong>pHLIP<sup>\u00ae<\/sup> Technology for Intracellular Delivery<\/strong><\/strong>: pHLIP peptides can be used for&nbsp;targeted intracellular delivery of therapeutic payloads (polar and moderately hydrophobic molecules)  to cytoplasm of metabolically active cells.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"alignleft size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-2.jpg\" alt=\"\" class=\"wp-image-515\" width=\"743\" height=\"349\" srcset=\"https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-2.jpg 990w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-2-300x141.jpg 300w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-2-768x361.jpg 768w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-2-364x171.jpg 364w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Reshetnyak-et-al-Figure-2-500x235.jpg 500w\" sizes=\"auto, (max-width: 743px) 100vw, 743px\" \/><figcaption>Image is from Reshetnyak et al., <em>Front Bioeng Biotechnol.<\/em> 2020<\/figcaption><\/figure><\/div>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p class=\"has-normal-font-size\"><strong>pHLIP<sup>\u00ae<\/sup> Nanotechnology<\/strong>: Multiple pHLIP&nbsp;peptides can be used to decorate a single nanoparticle, which can range in size from a few to hundreds of nanometers. Nanocarriers decorated with pHLIP&nbsp;peptides are biocompatible, can target tumors, and demonstrate enhanced cellular uptake by cancer cells. Among the pHLIP peptide-coated nanoparticles that have been investigated are lipid, polymer and metal-based nanomaterials.<\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"alignleft size-large is-resized\"><img decoding=\"async\" src=\"http:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-4-copy-1024x1007.jpg\" alt=\"\" class=\"wp-image-519\" width=\"600\" srcset=\"https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-4-copy-1024x1007.jpg 1024w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-4-copy-300x295.jpg 300w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-4-copy-768x756.jpg 768w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-4-copy-364x358.jpg 364w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-4-copy-500x492.jpg 500w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-4-copy-1000x984.jpg 1000w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-4-copy-1280x1259.jpg 1280w, https:\/\/physics.uri.edu\/biophysics\/wp-content\/uploads\/sites\/10\/2022\/04\/Figure-4-copy.jpg 1482w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption>Image is from Wyatt et al., <em>Trends Biotechnol.<\/em> 2017<\/figcaption><\/figure><\/div>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>pHLIP Technology pHLIP\u00ae technology constitutes family of pH-Low Insertion Peptides, a novel class of pH-sensitive delivery agents, which selectively target and deliver diagnostic and therapeutic molecules to tumors. pHLIPs are linear peptides that sense cell-surface pH. They are moderately hydrophobic 25-35 aa peptides containing protonatable carboxyl groups. At&nbsp; normal&nbsp; pH, pHLIP&nbsp;peptides exist&nbsp; in&nbsp; unstructured,&nbsp; coil [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-417","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/physics.uri.edu\/biophysics\/wp-json\/wp\/v2\/pages\/417","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/physics.uri.edu\/biophysics\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/physics.uri.edu\/biophysics\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/physics.uri.edu\/biophysics\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/physics.uri.edu\/biophysics\/wp-json\/wp\/v2\/comments?post=417"}],"version-history":[{"count":22,"href":"https:\/\/physics.uri.edu\/biophysics\/wp-json\/wp\/v2\/pages\/417\/revisions"}],"predecessor-version":[{"id":729,"href":"https:\/\/physics.uri.edu\/biophysics\/wp-json\/wp\/v2\/pages\/417\/revisions\/729"}],"wp:attachment":[{"href":"https:\/\/physics.uri.edu\/biophysics\/wp-json\/wp\/v2\/media?parent=417"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}