Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeted drug delivery now possible with ’pHLIP’ peptide

13.04.2006
Scientists at Yale and the University of Rhode Island report the development of a peptide that can specifically and directly deliver molecules to the inside of cells like a nanosyringe, creating a new tool for drug delivery, gene control and imaging of diseased tissues.

Their "cargo carrier" peptide called pHLIP, for pH (Low) Insertion Peptide, accumulates in the membranes of cells in acidic environments and spontaneously transfers attached molecules across the membrane. The cargo is then released by cleavage of a sulfur-sulfur bond that is only unstable if it is inside the cell. The study, published early online in the Proceedings of the National Academy of Sciences, was led by Donald M. Engelman, professor of molecular biophysics and biochemistry at Yale.


The delivery of fluorescent phalloidin into cells by pHLIP. (a) HeLa cells at pH 7.4 (Left) shows weak label localized at the cell membrane, and pH 6.5 (Right) shows fluorescent actin filaments inside cells. (b) HeLa (Left), breast cancer (Center), and prostate cancer (Right) cells show different and characteristic patterns of fluorescent actin filaments. Credit: Credit: Yale University

"Our system offers a new technology for the fast and efficient delivery of drugs, imaging probes, or cell and gene regulation agents into living cells," said Engelman. "pHLIP may provide a new approach for imaging, diagnosis and treatment of diseases with naturally occurring or artificially created low-pH extracellular environments, such as tumors, infarcts, stroke-afflicted tissue, atherosclerotic lesions, sites of inflammation or infection, or damaged tissue resulting from trauma."

Normal cells are surrounded by an environment with a constant pH of about 7.4, while tumor cells and sites of inflammation actively pump protons out and create an acid extracellular pH of 5.5 to 6.5.

The study shows that pHLIP entry into the cell membrane and the translocation of molecules into cells are not mediated by the usual entry pathways -- endocytosis, interactions with cell receptors, or by formation of pores in cell membranes.

"By translocating a molecule into a cell and releasing it in the cytoplasm, pHLIP functions, in effect, as a nanosyringe," according to Engelman. "The peptide does not exhibit any of this structure in solution or on the cell membrane at neutral pH. However, at low pH it becomes rigid like a syringe needle, inserts into a cell membrane, and injects molecules into cells.

Drug or dye molecules can be linked by sulfur-sulfur bonds to pHLIP. This paper demonstrates the effectiveness of pHLIP with a cargo of fluorescently tagged phalloidin, a toxin from the deadly Amanita phalloides mushroom that normally cannot enter cells. Inside the cells phalloidin binds to actin molecules and "freezes" the cellular skeleton giving a distinct visual pattern under the microscope.

Janet Rettig Emanuel | EurekAlert!
Further information:
http://www.yale.edu
http://www.yale.edu/ocr/

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>