Abstract

The treatment of brain-related disorders is limited by the presence of the blood–brain barrier (BBB), which highly regulate the crossing of drugs. Metal nanoparticles (NP) have unique features that could contribute to the development of therapies for these diseases. NP have the capacity to carry several molecules of a drug; furthermore, their unique physico- chemical properties allow, for example, photo thermal therapy to produce molecular surgery to destroy tumor cells and toxic structures.[1] However, the NP into the blood by dynamic interactions with the biological system conform a nano/bio interface called protein corona (PC) (Figure 1). These interactions could be the key for the modulation of biodistribution, excretion, immune response and metabolization of NM. So, the nature of NP will influence around nonspecific interactions with biological components. [2,3] In our group, we have obtained gold NP (AuNP) functionalized to peptides (conjugated) as the sequence CLPFFD for targeting to beta-amyloid (Aβ) involved in Alzheimer’s disease, and THRPPMWSPVWPCLPFFD, that include a shuttle that is recognized by the transferrin receptor in the blood brain barrier (BBB) thereby encouraging the transcytosis of the blood brain barrier (BBB) (Figure 2). [1] The conjugate AuNP-CLPFFD have been used to destroy the aggregates of Ab after irradiation with microwaves in vitro.[4] However, in vivo assays the conjugated had been accumulated mostly in liver and spleen due to the retention by the reticuloendothelial system (RES), affecting the availability of these NP to reach the brain.[5] So, the interaction of NP with plasmatic proteins leads to the PC that has influence in the pharmacokinetic behavior of the nanoparticles. In this work was evaluated the influence of the peptide functionalization of AuNP of 12 nm width in the formation of the PC. We recognized a great number of proteins bound to the NP, with small changes in the protein pattern, which is related with the fate of the NM in the body. The presence of certain biological proteins could contribute to crossing through the BBB. In this work we increased in vivo the brain delivery of AuNP by capping them with Apolipoprotein-E, a protein detected previously over CP that could contribute to crossing through the BBB by a receptor transcytosis mediated mechanisms in the BBB. These results are relevant for future pharmaceutical approaches because are useful to predict or understand the in vivo behavior of NM functionalized with different molecules and their pharmacokinetic behavior.