Peptides and proteins used to enhance gold nanoparticle delivery to the brain: preclinical approaches

Abstract

Carolina Velasco-Aguirre,1,2,* Francisco Morales,1,2,* Eduardo Gallardo-Toledo,1,2 Simon Guerrero,1,2 Ernest Giralt,3,4 Eyleen Araya,5 Marcelo J Kogan1,2 1Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 2Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile; 3Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain, 4Department of Organic Chemistry, University of Barcelona, Barcelona, Spain; 5Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andrés Bello, Andrés Bello, Santiago, Chile*These authors contributed equally to this work Abstract: An exciting and emerging field in nanomedicine involves the use of gold nanoparticles (AuNPs) in the preclinical development of new strategies for the treatment and diagnosis of brain-related diseases such as neurodegeneration and cerebral tumors. The treatment of many brain-related disorders with AuNPs, which possess useful physical properties, is limited by the blood–brain barrier (BBB). The BBB highly regulates the substances that can permeate into the brain. Peptides and proteins may represent promising tools to improve the delivery of AuNPs to the central nervous system (CNS). In this review, we summarize the potential applications of AuNPs to CNS disorders, discuss different strategies based on the use of peptides or proteins to improve the delivery of AuNPs to the brain, and examine the intranasal administration route, which bypasses the BBB. We also analyze the potential neurotoxicity of AuNPs and the perspectives and new challenges concerning the use of peptides and proteins to enhance the delivery of AuNPs to the brain. The majority of the work described in this review is in a preclinical stage of experimentation, or in select cases, in clinical trials in humans. We note that the use of AuNPs still requires substantial study before being translated into human applications. However, for further clinical research, the issues related to the potential use of AuNPs must be analyzed.Keywords: blood–brain barrier, central nervous system, transcytosis, drug delivery, EPR effect, biodistribution