20 November 2008

Tracer nanoparticles

One of the most important areas of applied research in today's medicine is the search for an effective and safe method of delivering medicines to certain areas of the body. Some of the developed methods are effective, but not always safe, others are quite safe, but often fail during delivery. The drug delivery technology developed by researchers from Penn State University using non-toxic nanoparticles appears to be free from these drawbacks, and allows you to control the delivery of drugs by the glow of fluorescent dyes released simultaneously with them.

A group of researchers of various specialties, including materials scientists, chemists, physicists, bioengineers and pharmacologists, have demonstrated that calcium phosphate particles with a size of 20-50 nanometers successfully pass into cells and dissolve, leaving their "cargo" (drug or dye) in the cell.

On the left, nanoparticles deliver a fluorescent dye to endothelial cells (in the bull's aorta), where a low pH level leads to the dissolution of calcium phosphate particles and the release of the dye. On the right – undissolved nanoparticles.

Measuring the activity of particles of this size requires special equipment. A group of students led by Associate Professor Peter Butler used high-frequency lasers to measure the size of particles containing fluorescent dyes, up to their complete dissolution. The method used is known in pulsed laser spectroscopy as counting single photons with time correlation, in which a high-frequency sequence of nanosecond laser pulses is used to determine the time or duration of fluorescence. The group was able to carry out laboratory measurements of particle sizes and their distribution in a saline solution with phosphate additives, which imitated the composition of blood.

The scientists' task was to change the initial neutral pH of the solution, identical to blood, to a more acidic medium, such as in the layers surrounding solid tumors. Moreover, the pH change had to be done precisely in those zones that are located directly in front of the membrane and are responsible for collecting nanoparticles and transferring them to the cell. As soon as the pH decreases, the acidic medium dissolves the calcium phosphate particles. During the dissolution process, scientists observed a decrease in the size of calcium phosphate nanoparticles down to the size of a drop of dye inside them, which allowed us to conclude that the pH reduction method was suitable for releasing any contents of the nanoparticles used.

Despite the fact that the initial goal of the experiments was the delivery of drugs for targeted cancer therapy, the group was also interested in working out the mechanism of delivery of various medications, in particular, for the treatment of vascular diseases, such as atherosclerosis and stenosis (narrowing) of blood vessels.

An experiment on the delivery of ceramide (a chemotherapy drug that initiates the death of cancer cells), optimized for both the treatment of cancer and for the treatment of vascular diseases, also had a positive result. Groups of Professors Mark Kester and Jong Yun from Penn State Milton S. Hershey Medical Center and Penn State College of Medicine at the University of Pennsylvania, using human vascular smooth muscles in vitro and the mechanism of drug delivery in calcium phosphate nanoparticles, managed to reduce the growth rate smooth muscle cells by 80%. At the same time, the drug doses were 25 times less than with the traditional administration of ceramide, and did not damage the cells.

The postman nanoparticles made of calcium phosphate were developed by a group of students led by Jim Adair, Professor of Materials Science and Engineering. These nanoparticles have a number of advantages that other drug delivery systems do not have. Unlike quantum dots, which mostly consist of toxic metals, calcium phosphate is a safe mineral that exists in nature and is present in the blood in fairly significant quantities. The method presented by the group of Prof. Adera differs in that it uses smaller particles, there is no agglomeration of nanoparticles (even in solution they are evenly distributed), drugs or dyes are injected into the particles (where they are protected), and do not use intricate ways of placing them on the surface of the agent particles. In addition, the proposed method of delivery and encapsulation does not require a large number of expensive drugs and dyes.

An interesting effect has been noted, for which scientists do not yet have an explanation: the dyes delivered to the object inside the nanoparticles have four times higher brightness than initially.

Work on simultaneous delivery of both drugs and dyes will allow creating a new method of controlled targeted drug delivery. The results of the research and the main ideas were published in the online edition of Nano Letters. The total number of researchers, including students who participated in the project, was about 200 people.

The project was supported by the National Endowment for Scientific Research, NASA and Keystone Nano, Inc. Part of the work was funded by targeted grants to the project participants.

The press release of Nanoparticles Deliver Their Cargo, Then Disappear is published on the MRI website.

Portal "Eternal youth" www.vechnayamolodost.ru based on NanoNewsNet materials 


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