Backpacks for monocytes
"Hitchhiking" to the area of inflammation
NanoNewsNet based on UCSB materials:
‘Cellular backpacks’ attached to white blood cells that target inflammation can provide therapy and relief for a host of conditions
Inflammation is a normal and often beneficial response to injury or infection. Edema, fever and even pain are all attempts by the body to protect its soft tissues, remove objects, substances or microorganisms that violate their integrity and initiate healing. However, constant inflammation is often an indicator of more complex diseases and can itself lead to serious problems, including deterioration of healing, loss of function or even tissue death.
"Many diseases lead to inflammation," says Samir Mitragotri, professor of chemical engineering at the University of California, Santa Barbara (UCSB) and director of the Center for Bioengineering.
Whether the inflammation is a by-product of the disease or it is itself a disease, in any case, this is a common indicator of problems with this system.
"If we could use this common denominator as a target, whether the cause of inflammation is cancer or arthritis, we could deliver a drug there," continues Mitragotri, who specializes in targeted drug delivery.
Using naturally occurring processes in the body, researchers from UCSB and the Massachusetts Institute of Technology (MIT) have developed a method for targeting inflamed tissues, creating a platform for the treatment of both inflammation and its causes.
"This is a cell-mediated approach to targeted drug delivery," explains UCSB graduate student Aaron Anselmo, lead author of a study published in the Journal of Controlled Release (Monocyte–mediated delivery of polymeric backpacks to inflamed tissues: a generalized strategy to deliver drugs to treat inflammation).
The key to the new technology is the use of monocytes, a type of white blood cells known for their ability to penetrate deep layers of tissue. Under normal conditions, the function of monocytes is to circulate in the blood and respond to biochemical signals indicating inflammation – a sign of injury or infection. Once in the zone of inflammation, monocytes differentiate into macrophages, cells located in the affected tissues and absorbing and digesting foreign material.
Working in collaboration with experts in the field of chemical technology and materials science from MIT, UCSB researchers have developed an approach based on "cellular backpacks" – flat, disc-shaped polymer particles that will be able, in the near future, to carry therapeutic agents and release them in the area of inflammation. On the one hand, these polymer disks are covered with a single layer of antibodies capable of binding to receptors on the surface of monocytes.
To get to their destination, disc-shaped microparticles use monocytes (photo: Peter Allen)
To prevent the absorption and destruction of the cellular backpack by the cell transporting it, the researchers chose a flexible particle, not spherical in shape, which, according to the study, turned out to be more durable and resistant to phagocytosis than a rigid spherical particle. The shape and flexibility allow the backpack to bind firmly to the cell, resisting phagocytosis, travel "hitchhiking" on monocytes and reach inflamed tissue.
In vitro and in vivo tests have proved that cell backpacks successfully attach to monocytes and are transported by them to problem areas without disturbing the natural functions of monocytes. Further research will consist in studying how much of the drug can be loaded into cellular backpacks. Ideally, the backpacks loaded with the drug will be injected into the blood, where they will bind to circulating monocytes and be transported by them to the areas of inflammation. Here they will immediately collapse and release their payload.
According to the researchers, this delivery system has great potential. "The main advantage here is that we can deliver the drug in a more effective dose," Professor Mitragotri comments on the development.
Take, for example, the case of chemotherapy, which often has a narrow therapeutic corridor: too little – and treatment is ineffective, too much – and it can lead to death. Since chemotherapeutic drugs are distributed through the blood and affect all tissues with which they come into contact, their doses are limited, at least partially, by the harmful effects they have on other intact organs and their functions. Targeted therapy can not only ensure the safety of other body systems, explains Mitragotri, but also allow the use of higher doses of drugs, which will shorten the treatment time.
Portal "Eternal youth" http://vechnayamolodost.ru16.01.2015