Brain-Penetrating Nanoparticles for Analysis of the Brain Microenvironment

The past decade has witnessed explosive growth in the development of nanoparticle-based therapies for the treatment of neurological disorders and diseases. The systemic delivery of therapeutic carriers to the central nervous system (CNS) is hindered by both the blood-brain barrier (BBB) and the porous and electrostatically charged brain extracellular matrix (ECM), which acts as a steric and adhesive barrier. Therapeutic delivery to the brain is influenced by changes in the brain microenvironment, which can occur as a function of physiology, biology, pathology, and developmental age. Brain-penetrating nanoparticles (BPNs) are an optimal platform not only for therapeutic delivery to the brain, but also for evaluating changes in the brain microenvironment. BPNs possess both the capability to readily move within their local environment to survey their surroundings and the ability to reach the diffuse disease cells often associated with CNS disorders. To achieve effective delivery of BPNs to specific locations within the brain requires careful control over the nanoparticle's transport properties. Here, we describe the process of conjugating a dense layer of poly(ethylene glycol) (PEG) to the surface of nonbiodegradable nanoparticles to achieve brain-penetrating capabilities.