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Platelet-Like Nanoparticles Boost Therapeutic Effects

Red blood cells and platelets

Red blood cells held together with platelets, in blue, and fibrin, in yellow. (NIH.gov)

16 September 2015. Engineers and medical researchers at University of California in San Diego designed biocompatible nanoparticles disguised as blood platelets, which they found increased the particles’ targeting and medicinal effects. The team led by engineering faculty Liangfang Zhang and Shu Chien published its proof-of-concept study today in the journal Nature (paid subscription required).

The UC-San Diego researchers are seeking to improve drug delivery of compounds needed in specific parts of the body, but otherwise require large and potentially dangerous doses for individuals taking the drugs if given as general systemic medications. To improve drug targeting, nanoscale particles, where 1 nanometer equals 1 billionth of a meter, are considered a promising method for drug delivery, since they can accumulate at disease sites with their drug payloads. Designers of nanoscale drug delivery systems, however, have been held back by the need for nanoparticles to be accepted by the body, and not trigger an immune reaction.

Zhang, Chien and colleagues devised their nanoparticles with a core of biocompatible polymer that the body can metabolize, infused with drug compounds. The team coated the particles with the membranes that surround blood platelets. The researchers separated the platelets from whole blood, then isolated the surface membranes  from the platelets. The membranes were then broken up and fused to the particles, each about 100 nanometers across.

The use of platelet membranes is an extension of earlier research by Zhang’s lab showing nanoscale sponges coated with red blood cell membranes could absorb and remove toxins such as bacteria, snake venom, and bee stings from the blood stream. Platelet membranes make it possible for nanoparticles to express their whole range of proteins and receptors, and thus interact like platelets in blood.

In the new study, the researchers tested their platelet-like nanoparticles with lab mice and rats. In one test, the team infused the particles with docetaxel, a chemotherapy drug, but also with the ability to prevent scar tissue from forming in the lining of blood vessels. The docetaxel-laden particles were given to rats with damaged arteries, and the team found the particles accumulated at the damage sites and repaired the arteries.

In a second test, particles were loaded with the antibiotic vancomycin and given to mice infected with methicillin-resistant Staphylococcus aureus or MRSA bacteria, the cause of dangerous and difficult to treat infections often found in hospitals. Although the dosage given the mice receiving the nanopartile treatments was one-sixth the normal scaled-down dose, mice receiving nanoparticles had bacterial counts one-thousandth that of mice given normal treatments of vancomycin.

The researchers believe that because of their improved targeting, the platelet-like nanoparticles offer an opportunity to lower dosages, while still boosting effectiveness of drugs other than antibiotics “While this proof of principle study demonstrates specific delivery of therapeutic agents to treat cardiovascular disease and bacterial infections,” says Chien in a university statement, “it also has broad implications for targeted therapy for other diseases such as cancer and neurological disorders.”

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