Researchers have discovered a way to coat therapeutic devices to enable them to pass through the body’s natural ‘security system’, designed to reject foreign objects that have entered the body, for better drug delivery.
The research, which was recently published in the journal Science, could help ‘foreign bodies’, such as pacemakers, artificial joints and nanoparticles designed to deliver drugs, to be accepted in the body more easily.
Researchers at the University of Pennsylvania School of Engineering and Applied Science and Penn’s Institute for Translational Medicine and Therapeutics have created a ‘passport’ for such therapeutic devices by coating them in a human protein that can pass through the body without being identified as foreign by the body.
The innate immune system tries to destroy or form a barrier to particles it doesn’t recognise as being part of the body, and drug-delivery nanoparticles naturally trigger this response.
In earlier research conducted in 2008, scientists discovered that the human protein CD47, found on almost all mammalian cell membranes, binds to a macrophage receptor known as SIRPa in humans. If a macrophage’s SIRPa binds to a cell’s CD47, it tells the macrophage that the cell isn’t an invader and should be allowed to proceed on.
Since the publication of this discovery, scientists have discovered how to computationally design the smallest sequence of amino acids that would act like CD47.
After chemically synthesising this minimal peptide, the team attached it to conventional nanoparticles that could be used in a variety of experiments and used mouse models to demonstrate better imaging of tumors, and as well as improved efficacy of an anti-cancer drug-delivery particles.
Though early days, the research team hope the ‘minimal peptide’ can be attached to a wide range of drug-delivery vehicles.
Graduate student Pia Rodriguez said; "From your body’s perspective, an arrowhead a thousand years ago and a pacemaker today are treated the same – as a foreign invader.
"We’d really like things like pacemakers, sutures and drug-delivery vehicles to not cause an inflammatory response from the innate immune system."
During the experiments, scientists used different fluorescent dyes on two kinds of nanoparticles and took blood samples every 10 minutes to measure how many particles of each kind were left.
"We injected the two particles in a 1-to-1 ratio and 20-30 minutes later, there were up to four times as many particles with the peptide left," Rodriguez added.
Chief conductor of the study professor, Dennis Discher, said the passport molecule can be made cleanly in a machine and easily modified during synthesis in order to attach to all sorts of implanted and injected things.
The research was supported by the National Institutes of Health, Penn’s Institute for Translational Medicine and Therapeutics, the National Science Foundation, Penn’sMaterials Research Science and Engineering Center and Penn’s Nano / Bio Interface Center.
Image: Scientists hope their research will aid the delivery of nanoparticles.
