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A protein ‘passport’ that helps nanoparticles get past immune system

A protein ‘passport’ that helps nanoparticles get past immune system | Longevity science | Scoop.it

Macrophages — literally, "big eaters" — are a main part of the body's innate immune system . These cells find and engulf invaders, like bacteria, viruses, splinters and dirt. Unfortunately, macrophages also eat helpful foreigners, including nanoparticles that deliver drugs or help image tumors.


Along with members of his lab, Dennis Discher, professor of chemical and biomolecular engineering in the School of Engineering and Applied Science, has developed a "passport" that could be attached to therapeutic particles and devices, tricking macrophages into leaving them alone. 

Taking a cue from a membrane protein that the body's own cells use to tell macrophages not to eat them, the researchers engineered a the simplest functional version of that protein and attached it to plastic nanoparticles. These passport-carrying nanoparticles remained in circulation significantly longer than ones without the peptide, when tested in a mouse model.


In 2008, Discher’s group showed that the human protein CD47, found on almost all mammalian cell membranes, binds to a macrophage receptor known as SIRPa in humans. Like a patrolling border guard inspecting a passport, 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.

 

“There may be other molecules that help quell the macrophage response,” Discher said. “But human CD47 is clearly one that says, ‘Don’t eat me’.” Since the publication of that study, other researchers determined the combined structure of CD47 and SIRPa together. Using this information, Discher’s group was able to computationally design the smallest sequence of amino acids that would act like CD47. This “minimal peptide” would have to fold and fit well enough into the receptor of SIRPa to serve as a valid passport. After chemically synthesizing this minimal peptide, Discher’s team attached it to conventional nanoparticles that could be used in a variety of experiments. “Now, anyone can make the peptide and put it on whatever they want,” Rodriguez said.

 

The research team’s experiments used a mouse model to demonstrate better imaging of tumors and as well as improved efficacy of an anti-cancer drug-delivery particle.

 

As this minimal peptide might one day be attached to a wide range of drug-delivery vehicles, the researchers also attached antibodies of the type that could be used in targeting cancer cells or other kinds of diseased tissue. Beyond a proof of concept for therapeutics, these antibodies also served to attract the macrophages’ attention and ensure the minimal peptide’s passport was being checked and approved.


Video is here: http://tinyurl.com/b6dthgb


Via Dr. Stefan Gruenwald
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Drug-delivery nanoparticles mimic white blood cells to avoid immune rejection | KurzweilAI

Drug-delivery nanoparticles mimic white blood cells to avoid immune rejection | KurzweilAI | Longevity science | Scoop.it

Scientists at The Methodist Hospital Research Institute have found a possible way to fool the immune system to prevent it from recognizing and destroying nanoparticles before they deliver their drug payloads.

 

“Our goal was to make a particle that is camouflaged within our bodies and escapes the surveillance of the immune system to reach its target undiscovered,” said Department of Medicine Co-Chair Ennio Tasciotti, Ph.D., the study’s principal investigator.

 

 

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Gold nanoparticle could allow powerful alpha particles to join cancer fight

Gold nanoparticle could allow powerful alpha particles to join cancer fight | Longevity science | Scoop.it

Gold nanoparticles have already shown promise in precisely highlighting brain tumors, “blowing up” individual diseased cells, and developing a lung cancer breath test. Now researchers have created gold nanoparticles that allow an alpha particle-emitting element to be directed to small cancer tumors. The researchers say the gold coating keeps the powerful radioactive particles in place at the cancer site so they do negligible damage to healthy organs and tissue.

 

 

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Gold nanoparticle prostate cancer treatment targets without collateral damage (animal tests) | KurzweilAI

Gold nanoparticle prostate cancer treatment targets without collateral damage (animal tests) | KurzweilAI | Longevity science | Scoop.it

Animal studies have been conducted successfully using gold nanoparticles to target prostate cancer tumors. Next step-- human trials...

 

Current treatments for prostate cancer are not effective in patients who have aggressive prostate cancer tumors. Most of the time, prostate cancers are slow-growing; the disease remains localized and it is easily managed. However, aggressive forms of the disease spread to other parts of the body, and is the second-leading cause of cancer deaths in U.S. men.

 

The MU scientists believe their treatment will be able to shrink aggressive tumors or eliminate them completely. Axiak-Bechtel says this treatment can be safe and effective in dogs as well as humans because dogs are the only other mammal to naturally contract the aggressive form of prostate cancer.

 

 

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