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Platelet mimics provide targeted drug delivery

Platelet-membrane-coated

nanoparticles binding to the

lining of a damaged artery

Image courtesy of the

Zhang Research Group

Nanoparticles disguised as human platelets can provide targeted drug delivery, according to research published in Nature.

The nanoparticles are made of a biodegradable polymer coated with human platelet membranes.

This coating allows the nanoparticles to circulate in the bloodstream without being attacked by the immune system and to preferentially bind to damaged blood vessels and certain pathogens.

Murine experiments showed that these platelet-mimicking nanoparticles can deliver drugs to targeted sites, thereby increasing the therapeutic effect.

“Because of their targeting ability, platelet-mimicking nanoparticles can directly provide a much higher dose of medication specifically to diseased areas without saturating the entire body with drugs,” said study author Liangfang Zhang, PhD, of the University of California San Diego.

Creating the platelet mimics

To make the nanoparticles, Dr Zhang and his colleagues first separated platelets from whole blood samples using a centrifuge. The platelets were then processed to isolate the membranes from the platelets.

Next, the platelet membranes were broken up into much smaller pieces and fused to the surface of the nanoparticle cores. The resulting platelet-membrane-coated nanoparticles were approximately 100 nanometers in diameter.

This cloaking technology is based on a strategy Dr Zhang’s group had developed to cloak nanoparticles in red blood cell membranes. The researchers previously demonstrated that nanoparticles disguised as red blood cells are capable of removing toxins from the bloodstream.

With the current work, the researchers were able to produce platelet mimics that contain the complete set of surface receptors, antigens, and proteins naturally present on platelet membranes.

“Our technique takes advantage of the unique natural properties of human platelet membranes, which have a natural preference to bind to certain tissues and organisms in the body,” Dr Zhang said.

This targeting ability, which red blood cell membranes do not have, makes platelet membranes extremely useful for targeted drug delivery, according to the researchers.

Platelet mimics at work

The researchers packed the platelet-mimicking nanoparticles with docetaxel, a drug used to prevent scar tissue formation in the lining of damaged blood vessels, and administered them to rats afflicted with injured arteries.

The docetaxel-containing nanoparticles collected at the damaged sites of arteries and healed them.

The researchers then injected nanoparticles containing one-sixth the clinical dose of the antibiotic vancomycin into a group of mice systemically infected with methicillin-resistant Staphylococcus aureus bacteria.

Bacterial counts in the organs of these mice were up to 1000 times lower than in mice treated with the clinical dose of vancomycin alone.

“Our platelet-mimicking nanoparticles can increase the therapeutic efficacy of antibiotics because they can focus treatment on the bacteria locally without spreading drugs to healthy tissues and organs throughout the rest of the body,” Dr Zhang said. “We hope to develop platelet-mimicking nanoparticles into new treatments for systemic bacterial infections and cardiovascular disease.”

Dr Zhang noted that this drug delivery technique could potentially be used in other diseases as well, including cancers.

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Platelet-membrane-coated

nanoparticles binding to the

lining of a damaged artery

Image courtesy of the

Zhang Research Group

Nanoparticles disguised as human platelets can provide targeted drug delivery, according to research published in Nature.

The nanoparticles are made of a biodegradable polymer coated with human platelet membranes.

This coating allows the nanoparticles to circulate in the bloodstream without being attacked by the immune system and to preferentially bind to damaged blood vessels and certain pathogens.

Murine experiments showed that these platelet-mimicking nanoparticles can deliver drugs to targeted sites, thereby increasing the therapeutic effect.

“Because of their targeting ability, platelet-mimicking nanoparticles can directly provide a much higher dose of medication specifically to diseased areas without saturating the entire body with drugs,” said study author Liangfang Zhang, PhD, of the University of California San Diego.

Creating the platelet mimics

To make the nanoparticles, Dr Zhang and his colleagues first separated platelets from whole blood samples using a centrifuge. The platelets were then processed to isolate the membranes from the platelets.

Next, the platelet membranes were broken up into much smaller pieces and fused to the surface of the nanoparticle cores. The resulting platelet-membrane-coated nanoparticles were approximately 100 nanometers in diameter.

This cloaking technology is based on a strategy Dr Zhang’s group had developed to cloak nanoparticles in red blood cell membranes. The researchers previously demonstrated that nanoparticles disguised as red blood cells are capable of removing toxins from the bloodstream.

With the current work, the researchers were able to produce platelet mimics that contain the complete set of surface receptors, antigens, and proteins naturally present on platelet membranes.

“Our technique takes advantage of the unique natural properties of human platelet membranes, which have a natural preference to bind to certain tissues and organisms in the body,” Dr Zhang said.

This targeting ability, which red blood cell membranes do not have, makes platelet membranes extremely useful for targeted drug delivery, according to the researchers.

Platelet mimics at work

The researchers packed the platelet-mimicking nanoparticles with docetaxel, a drug used to prevent scar tissue formation in the lining of damaged blood vessels, and administered them to rats afflicted with injured arteries.

The docetaxel-containing nanoparticles collected at the damaged sites of arteries and healed them.

The researchers then injected nanoparticles containing one-sixth the clinical dose of the antibiotic vancomycin into a group of mice systemically infected with methicillin-resistant Staphylococcus aureus bacteria.

Bacterial counts in the organs of these mice were up to 1000 times lower than in mice treated with the clinical dose of vancomycin alone.

“Our platelet-mimicking nanoparticles can increase the therapeutic efficacy of antibiotics because they can focus treatment on the bacteria locally without spreading drugs to healthy tissues and organs throughout the rest of the body,” Dr Zhang said. “We hope to develop platelet-mimicking nanoparticles into new treatments for systemic bacterial infections and cardiovascular disease.”

Dr Zhang noted that this drug delivery technique could potentially be used in other diseases as well, including cancers.

Platelet-membrane-coated

nanoparticles binding to the

lining of a damaged artery

Image courtesy of the

Zhang Research Group

Nanoparticles disguised as human platelets can provide targeted drug delivery, according to research published in Nature.

The nanoparticles are made of a biodegradable polymer coated with human platelet membranes.

This coating allows the nanoparticles to circulate in the bloodstream without being attacked by the immune system and to preferentially bind to damaged blood vessels and certain pathogens.

Murine experiments showed that these platelet-mimicking nanoparticles can deliver drugs to targeted sites, thereby increasing the therapeutic effect.

“Because of their targeting ability, platelet-mimicking nanoparticles can directly provide a much higher dose of medication specifically to diseased areas without saturating the entire body with drugs,” said study author Liangfang Zhang, PhD, of the University of California San Diego.

Creating the platelet mimics

To make the nanoparticles, Dr Zhang and his colleagues first separated platelets from whole blood samples using a centrifuge. The platelets were then processed to isolate the membranes from the platelets.

Next, the platelet membranes were broken up into much smaller pieces and fused to the surface of the nanoparticle cores. The resulting platelet-membrane-coated nanoparticles were approximately 100 nanometers in diameter.

This cloaking technology is based on a strategy Dr Zhang’s group had developed to cloak nanoparticles in red blood cell membranes. The researchers previously demonstrated that nanoparticles disguised as red blood cells are capable of removing toxins from the bloodstream.

With the current work, the researchers were able to produce platelet mimics that contain the complete set of surface receptors, antigens, and proteins naturally present on platelet membranes.

“Our technique takes advantage of the unique natural properties of human platelet membranes, which have a natural preference to bind to certain tissues and organisms in the body,” Dr Zhang said.

This targeting ability, which red blood cell membranes do not have, makes platelet membranes extremely useful for targeted drug delivery, according to the researchers.

Platelet mimics at work

The researchers packed the platelet-mimicking nanoparticles with docetaxel, a drug used to prevent scar tissue formation in the lining of damaged blood vessels, and administered them to rats afflicted with injured arteries.

The docetaxel-containing nanoparticles collected at the damaged sites of arteries and healed them.

The researchers then injected nanoparticles containing one-sixth the clinical dose of the antibiotic vancomycin into a group of mice systemically infected with methicillin-resistant Staphylococcus aureus bacteria.

Bacterial counts in the organs of these mice were up to 1000 times lower than in mice treated with the clinical dose of vancomycin alone.

“Our platelet-mimicking nanoparticles can increase the therapeutic efficacy of antibiotics because they can focus treatment on the bacteria locally without spreading drugs to healthy tissues and organs throughout the rest of the body,” Dr Zhang said. “We hope to develop platelet-mimicking nanoparticles into new treatments for systemic bacterial infections and cardiovascular disease.”

Dr Zhang noted that this drug delivery technique could potentially be used in other diseases as well, including cancers.

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