Exploiting microorganism biomimicry to interact with critical blood-tissue barriers

利用微生物仿生学与关键的血液组织屏障相互作用

• 批准号: RGPIN-2018-06636
• 负责人: ROULLIN, VGaëlle
• 金额: $ 2.04万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714371
• 关键词: Exploiting; microorganism; biomimicry; interact; critical

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.

虽然纳米粒子是非常有前途的药物输送系统，但在携带有效剂量的药物到某些组织区域方面，纳米粒子并没有被证明是有效的。例如，将药物用于大脑，治疗脑肿瘤或阿尔茨海默病仍然非常困难。其主要原因在于这些组织周围存在保护屏障。这些屏障由构成血管壁的内皮细胞构成，并由其他细胞层加强。因此，组织被保护免受一般毒性。不幸的是，在血液中循环的药物，无论是游离的还是装入纳米颗粒的，都很难穿过这些屏障。