**5. Nanoparticles and the brain**

One of the most promising potential applications is the design and synthesis of nanoparticles with characteristics that make them capable of crossing the BBB, thus allowing drugs (or even genes) to be taken directly to the CNS, exerting their therapeutic action at that site; this has the potential to offer alternatives to improve the quality of life of millions of people suffering from diseases that do not respond to treatment with conventional drugs and who usually receive doses that generate undesirable side effects derived from the toxicity of the drug itself [18, 27]. Another interesting application related to the brain is that given the ease of exosomes to diffuse freely through the BBB and circulate in different body fluids, and the fact that exosomes reflect the environment of the cell from which they originate, biosensors can take advantage to detect exosomes derived from cells with various CNS pathologies either cancer or neurodegenerative diseases [26, 28].

Unfortunately, the passage of nanoparticles into the brain implies that they can interact with neural cells, with the positive and negative consequences that this can have; although pollutant nanoparticles were previously described as possible causative agents of neurodegenerative diseases, it is a reality that any nanomaterial, depending on its characteristics and their biocorona could have the capacity to form ROS or promote inappropriate protein folding. Even more serious is that the harmful effects may be greater in the long term and related to the dose increase, since many of these materials will not be able to be eliminated from the site where they are deposited, exerting their negative effects indefinitely [8].

Of equal concern is that nanomaterials can induce changes in miRNAs, histones, and DNA methylation, producing changes in gene expression patterns that will not necessarily be beneficial and studies that contemplate identifying toxicity of nanomaterials for biomedical use should include an analysis of changes in gene expression to identify possible mechanisms of damage and/or cause of various diseases among which will, of course, include neurodegenerative diseases [8, 29].
