An earlier paper from the same groups shows that at low pH, pHLIP can move cell-impermeable molecules across a cell membrane, where they are released in the cytoplasm. “pHLIP acts as a molecular nanosyringe, inserting itself into the cell membrane and injecting compounds into cell,?said co-author Yana Reshetnyak, of the University of Rhode Island. “The transported molecules can be therapeutic or toxic to the cell, depending on the intended outcome—for treating cancer, the idea is to cause cell death.?
In addition to targeting tumors, other disease states that produce inflammation and cause tissue to be acidic are a target for pHLIP. “Acidosis is a physiological marker of many diseases ?and pHLIP feels acidity,?said Reshetnyak. “Therefore, pHLIP could also be used for monitoring of disease development and therapeutic outcomes. It might play very important role in the study of arthritis, ischemia and stroke.?
Lead author Oleg Andreev said, “We believe that universal medical tests to reveal many health problems at earlier stages may be developed based on pHLIP technology?
“Our discovery is an example of the reason that the NIH and DOD support basic science—we were working on the principles of membrane protein folding, and made a discovery with important medical implications that wouldn’t have happened without the ideas and approaches used in that work,?Engelman said.
Among the applications the team is actively pursuing are PET imaging of tumors, treatment of breast cancer, and alternative designs using the principles they have already established.