Molecular syringe delivers drug into cells

By Dr Matt Wilkinson

- Last updated on GMT

A 'homing' protein fragment that can track down tumours in the body
has been developed to deliver imaging agents or anticancer
therapies to cells.

Researchers from Yale University and the University of Rhode Island in the US have used the pHLIP (pH low insertion peptide) protein fragment to target the acidic tissue that builds up in tumours and inflammation sites observed in arthritis patients.

After attaching itself to a cell membrane the acidic conditions surrounding tumour cells cause the protein to change conformation and insert itself across the cell membrane and inject its payload.

The use of the pHILP protein fragment, in delivering drugs or imaging agents to tumours will be published in an upcoming issue of the Proceedings of National Academy of Sciences.

"Since the mechanism is general, and since even very small tumours can be targeted, there is an exciting array of possible applications for pHLIP," said Professor Donald Engelman, of Yale University and a co-author of the paper.

"We are very excited by the possibilities for both imaging and treating tumours."

This latest research used near-infrared (NIR) fluorescence to follow the accumulation of fluorescently-labelled pHILP at the site of acidic tissues in mouse cancer and inflammatory arthritis models.

Light in the NIR region can travel through tissue for several centimetres and allows the imaging of tumours or plaques in living models to allow disease progression to be monitored.

The technique was so effective that it enabled imaging of tumour spots of various sizes - even those that were too small to detect visually.

An earlier paper published by the groups in Biochemistry showed that at low pH, pHILIP can release cell-impermeable molecules into the cytoplasm inside acidic cells.

"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."

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