Drugs delivered by nanoparticles hold promise for targeted treatment ... However, the particles have to be injected into patients, which has limited their usefulness so far.
Now, researchers
from the Massachusetts Institute of Technology (MIT) and Brigham and Women’s
Hospital (BWH) have developed a new type of nanoparticle that can be delivered
orally and absorbed through the digestive tract, allowing patients to simply
take a pill …The new nanoparticles are coated with antibodies that act as a key
to unlock receptors found on the surfaces of cells that line the intestine,
allowing the nanoparticles to break through the intestinal walls and enter the
bloodstream.
“The key challenge is how to make a
nanoparticle get through this barrier of cells. Whenever cells want to form a
barrier, they make these attachments from cell to cell, analogous to a brick
wall Farokhzad said.
Researchers have
previously tried to break through this wall by temporarily disrupting the tight
junctions To build nanoparticles that can selectively break through the
barrier, the researchers took advantage of previous work that revealed how
babies absorb antibodies from their mothers’ milk, boosting their own immune
defenses. Those antibodies grab onto a cell surface receptor called the FcRN,
granting them access through the cells of the intestinal lining into adjacent
blood vessels.
The researchers
coated their nanoparticles with Fc proteins—the part of the antibody that binds
to the FcRN receptor, which is also found in adult intestinal cells. “It
illustrates that we can use these receptors to traffic nanoparticles that could
contain pretty much anything. Any molecule that has difficulty crossing the
barrier could be loaded in the nanoparticle and trafficked across,” Karnik
said. .. including designing nanoparticles that can cross other barriers, such
as the blood-brain barrier, which prevents many drugs from reaching the brain.
.
Date: December 2,
2013
Source: MIT
Drug Delivery: Why Gold
Nanoparticles Can Penetrate Cell Walls
Now, researchers at MIT and the Ecole Polytechnique de Lausanne inSwitzerland have figured out how
the process works, and the limits on the sizes of particles that can be used.
Their analysis appears in the journal Nano
Letters, by Reid Van Lehn,
Until now, says Van Lehn, the paper's lead author, "the mechanism was unknown. … In this work, we wanted to simplify the process and understand the forces" that allow gold nanoparticles to penetrate cell walls without permanently damaging the membranes or rupturing the cells.there is a limit concerning threshold that depends on the composition of the particle's coating.
The coating applied to the gold particles consists of a mix of hydrophobic and hydrophilic components that form a monolayer -- a just one molecule thick -- on the particle's surface.
Since the nanoparticles themselves are completely coated, and shaped in such a way that allows the nanoparticles to pass through the membrane and than seal the opening as soon as the particle has passed. "They would go through without allowing even small molecules to leak through behind them," Van Lehn says.
Irvine says that his lab is also interested in harnessing this
cell-penetrating mechanism as a way of delivering drugs to the cell's interior,
by binding them to the surface coating material. One important step in making
that a useful process, he says, is finding ways to allow the nanoparticle
coatings to be selective about what types of cells they attach to including biosensing molecules on or into certain cells,
Van Lehn says. In this way, scientists could detect or monitor specific
biochemical markers including a person’s brainwaves
Drug Delivery: Why Gold
Nanoparticles Can Penetrate Cell Walls
Aug.
22, 2013 — Cells are very good at protecting their precious contents --
and as a result, it's very difficult to penetrate their membrane walls to deliver drugs, nutrients or
biosensors without damaging or destroying the cell. One effective way of
doing so, discovered in 2008, is to use nanoparticles of pure gold, coated with
a thin layer of a special polymer. But nobody knew exactly why this combination
worked so well, or how it made it through the cell wall.
Now, researchers at MIT and the Ecole Polytechnique de Lausanne in
Until now, says Van Lehn, the paper's lead author, "the mechanism was unknown. … In this work, we wanted to simplify the process and understand the forces" that allow gold nanoparticles to penetrate cell walls without permanently damaging the membranes or rupturing the cells.there is a limit concerning threshold that depends on the composition of the particle's coating.
The coating applied to the gold particles consists of a mix of hydrophobic and hydrophilic components that form a monolayer -- a just one molecule thick -- on the particle's surface.
Since the nanoparticles themselves are completely coated, and shaped in such a way that allows the nanoparticles to pass through the membrane and than seal the opening as soon as the particle has passed. "They would go through without allowing even small molecules to leak through behind them," Van Lehn says.
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