VIEWPOINT www.nature.com/clinicalpractice/neuro Nanotechnology is an emerging interdisciplinary area of science and engineering with considerable potential for changing how we manipulate and control materials and devices at the molecular level (usually defined within the range of 1–100 nm), using physical or chemical methods, or both. This engineering results in functional properties that are not present in the constituent molecular building blocks that make up a nanotechnology device. Nanotechnologies are, therefore, defined on the basis of their functional properties rather than their chemical or physical make-up. Although at times a source of confusion, it is this functional, or engineering, definition that makes nanotechnology distinct from chemistry. Applications of nanotechnology to medicine complement other approaches for the diagnosis, treatment and study of disease. In neurology, in particular as it relates to the treatment of CNS disorders, nanotechnologies have the potential to contribute substantially to novel approaches for treating traumatic, degenerative and neoplastic disorders that are clinically difficult to manage. The clinical challenges imposed by the CNS and the obstacles faced by anything designed to target and interface with it are, to a large degree, a result of its unique anatomy and physiology—that is, its computational and physiological complexity and its highly restricted anatomical access. For example, in an ideal situation, a drug, oligo- nucleotide, functionalized nanoparticle or any other molecular species administered systemi- cally (e.g. intravenously) would first need to reach the blood–brain barrier while producing minimal systemic effects. It would then need to successfully cross the blood–brain barrier with minimal disruption to the barrier. Once in, the drug needs to selectively target its intended cell or ligand, and only then carry out its primary active function, whatever that might be (e.g. modifying the action of an enzyme, producing a new protein, or blocking or augmenting a receptor). It is diffi- cult, if not impossible, for any single drug or small molecule to accomplish all of these functions. Nanoengineered molecular complexes, however, What impact will nanotechnology have on neurology? Gabriel A Silva GA Silva is an Assistant Professor in the Departments of Bioengineering and Ophthalmology and the Neurosciences Program at the University of California, San Diego, CA, USA. Correspondence Departments of Bioengineering and Ophthalmology and Neurosciences Program University of California, San Diego Jacobs Retina Center, 0946 9415 Campus Point Drive La Jolla CA 92037–0946 USA gsilva@ucsd.edu Received 10 October 2006 Accepted 14 February 2007 www.nature.com/clinicalpractice doi:10.1038/ncpneuro0466 might be particularly well suited to addressing these challenges, because they can be designed to perform multiple functions in a coordinated way. Within the framework of a nanoengineered complex, the drug, protein or oligonucleotide that is intended to carry out the primary therapeutic function becomes one element of the complex, with other specific properties intended to address other challenges, such as delivering the complex, clearing it from the CNS or achieving the cooperation of multiple therapeutic compounds. Although no nanoengineered system designed to interact with the CNS has reached this level of sophistication, significant and exciting progress is being made. Several synthetic formulations— including PEG (polyethylene glycol), PLGA (poly[lactic-co-glycolic acid]) and poly(butyl- cyanoacrylate) polysorbate nanoparticles—are being investigated as potential carriers for drugs of various classes, including antineoplastics such as paclitaxel 1 and doxorubicin, 2 analgesics such as dalargin, 3 the trypanocidal agent diminazene, 4 and oligonucleotides and genes for gene therapy. 5 The aim is that biomimetic strategies incorporated into the designs of the nanoparticles will enable more- efficient delivery of the drugs by ‘tricking’ the body. For example, paclitaxel has been encapsulated in PLGA nanoparticles to produce a combined delivery and therapeutic nanoparticle system with controlled pharmacokinetics. Paclitaxel must be clinically delivered in a vehicle because of its insolubility under physiological conditions. The vehicle used conventionally, however, produces a number of serious adverse effects. By contrast, the size, chemical composition and surface coating of biodegradable polymer nanoparticles can be care- fully controlled and optimized to permit targeted delivery across the blood–brain barrier with reduced adverse effects, and might even enable further optimization to meet patient-specific requirements (i.e. personalized chemotherapy). 1 In vitro experiments with 29 different cancer cell lines that included neural as well as non-neural cells have demonstrated a targeted cytotoxicity of PLGA-encapsulated paclitaxel that was 13 times 180 NATURE CLINICAL PRACTICE NEUROLOGY APRIL 2007 VOL 3 NO 4