Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing.
Adrian JosephClaudia ContiniDenis CecchinSophie NybergLorena Ruiz-PérezJens GaitzschGavin FullstoneXiaohe TianJuzaili AziziJane E PrestonGiorgio VolpeGiuseppe BattagliaPublished in: Science advances (2017)
In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano- or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro- and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor-related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems.
Keyphrases
- blood brain barrier
- low density lipoprotein
- blood glucose
- cerebral ischemia
- endothelial cells
- cancer therapy
- drug delivery
- gene expression
- working memory
- white matter
- hydrogen peroxide
- blood pressure
- metabolic syndrome
- binding protein
- ionic liquid
- water soluble
- nitric oxide
- induced pluripotent stem cells
- functional connectivity
- solid state
- subarachnoid hemorrhage
- high resolution
- glycemic control