pHLIP, Inc. was founded to bring its proprietary pHLIP® Platform Technology to the clinic, aiming to improve the treatment of diseases where visualization and targeted therapy would be highly advantageous. The possible applications of the technology are wide-ranging, including cancer, inflammation and fibrosis.
Targeting
pHLIP® senses low pH at cell surfaces
pHLIP® binds weakly to cells with normal cell surface pH and is eventually washed away
When pHLIP® encounters low pH at cell surfaces, it inserts across cell membranes to deliver a payload into the cytoplasm or to locate a payload at the cell surface
Low pH targeting of solid tumors by pHLIP® agents has been shown in humans
Cytoplasmic Delivery
pHLIP® inserts across the cell membrane via a fast and cooperative coil-helix transition (membrane-associated folding)
The energy released during the pHLIP® insertion facilitates the transfer of a wide range of payloads, including large and polar molecules, across plasma or endosomal membranes directly into the cytoplasm.
Cell-impermeable polar payloads can be delivered into cells by pHLIP®
Most proteins that are located across membranes have one or more helical segments that cross the lipid bilayer, and studies of these helical parts in a highly researched protein, bacteriorhodopsin, revealed that one of the helices could fold from a disorganized state outside of a membrane to form a helix across the membrane in response to local acidity.
Because cell surfaces are acidic in tumors and inflamed tissues, versions of pHLIP® peptides were studied and tested as possible tumor targeting agents at Yale, the University of Rhode Island, the Memorial Sloan Kettering Cancer Center and many other Institutions. These studies showed that a large variety of cargoes can be targeted to cell surfaces or delivered across membranes into cells if their surfaces are acidic, creating opportunities to detect and treat acidic diseased tissues.
The licenses include exclusive Worldwide commercial rights to the linear and cyclic pH peptides patent families and pHLIP® trademark.