Engineering advanced nanomedicines against central nervous system diseases

Despite the impressive strides in the research community, numerous obstacles pose marked challenges in the treatment of central nervous system (CNS) disorders. The limitations of current therapeutics are primarily attributed to the systemic and local barriers, particularly the intact blood-brain barriers (BBB). Nanomedicine represents one promising avenue, which enables safe and effective delivery of neurotherapeutics into the CNS by traversing or bypassing the physical barriers. Here, we provide an overview of recent progress of advanced nanoengineering technologies for delivery of neurotherapeutics and elucidate how the emerging nanotherapeutics overcome the restrictive barriers with enhanced therapeutic implications to CNS diseases. The non-invasive strategies crossing BBB mainly comprise carrier-mediated transport, cell-mediated transport, adsorptive mediated transport, paracellular transport, passive diffusion, and receptor-mediated transport. We briefly discuss the typical paradigms of nanomaterials and their physiochemical factors determining CNS transport efficacy, particularly focusing on the applications of advanced nanotechnology in the management of ischemic stroke, neurodegenerative diseases, infectious diseases, pain, and tumor. The prospects and challenges of neuro-nanotherapeutics toward clinical translation are also analyzed from our point of view.