Exploiting microorganism biomimicry to interact with critical blood-tissue barriers

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Although very promising drug delivery systems, nanoparticles have failed to prove efficient in carrying effective amounts of drugs to certain tissue areas. For instance, it is still very difficult to address drugs to the brain, to cure brain tumors or Alzheimer's disease. The main reason lies in the existence of a protective barrier around those tissues. These barriers are constituted from endothelial cells making up the vessel walls, and are reinforced by other cell layers. Hence the tissues are protected from general toxicity. Unfortunately, it is very difficult for drugs circulating in the blood, either free or loaded into nanoparticles, to cross those barriers. On the other hand, some pathogens like viruses and bacteria (which are physically similar to nanoparticles) are able to cross those complex blood-tissue barriers. For example, HIV-1 (the virus responsible for AIDS) can infect the brain tissue. One way used by this virus is to attach very strongly via specific entry points (e.g. receptors) to the membrane of endothelial cells. The virus envelope contains a protein that is able to bind twice at the same time onto the cell membrane. As a consequence of this strong binding, the cell uptakes the viral particle and transports it, intact, to the other side. This program intends to mimic this behaviour and trigger a complete transport of nanoparticles across complex blood-tissue barriers, without deterioration. To that end, we will synthetize nanoparticles bearing two different elements of recognition acting cooperatively on two separate co-receptors of the endothelial cell membranes. Using HIV as a model, we will assemble those mimetic particles and screen them on cell cultures to determine their efficacy. Later, we will use the best formulations in mice, in order to transfer anticancer, antiviral or psychotropic drugs into the brain tissue. This kind of doubly-decorated nanoparticles could also be used to transfer higher quantity of antiretroviral drugs from the maternal blood to the breastfeeding milk of HIV-positive newborns. If successful, this program should provide powerful tools to understand infectious diseases and the transfer of substances from mother to child through breastfeeding.