LRP-1 functionalized polymersomes enhance the efficacy of carnosine in experimental stroke
Eun Sun Kim, Dong‐Min Kim, Sophie Nyberg, Alessandro Poma, Denis Cecchin, Saurabh Jain, Kyeong-A Kim, Young‐Jun Shin, Eun-Hye Kim, Minyeong Kim, Seung‐Hoon Baek, Jin‐Ki Kim, Thorsten R. Doeppner, Ali Ali, Jessica Redgrave, Giuseppe Battaglia, Arshad Majid, Ok‐Nam Bae
Abstract
Stroke is one of the commonest causes of death with limited treatment options. L-Carnosine has shown great promise as a neuroprotective agent in experimental stroke, but translation to the clinic is impeded by the large doses needed. We developed and evaluated the therapeutic potential of a novel delivery vehicle which encapsulated carnosine in lipoprotein receptor related protein-1 (LRP-1)-targeted functionalized polymersomes in experimental ischemic stroke. We found that following ischemic stroke, polymersomes encapsulating carnosine exhibited remarkable neuroprotective effects with a dose of carnosine 3 orders of magnitude lower than free carnosine. The LRP-1-targeted functionalization was essential for delivery of carnosine to the brain, as non-targeted carnosine polymersomes did not exhibit neuroprotection. Using Cy3 fluorescence in vivo imaging, we showed that unlike non-targeted carnosine polymersomes, LRP-1-targeted carriers accumulated in brain in a time dependent manner. Our findings suggest that these novel carriers have the ability to deliver neuroprotective cargo effectively to the brain.