International Journal of Nanomedicine (Dec 2019)
Characterization Of Blood–Brain Barrier Crossing And Tumor Homing Peptides By Molecular Dynamics Simulations
Abstract
Caterina Arcangeli,1 Chiara Lico,2 Selene Baschieri,2 Mariateresa Mancuso3 1Laboratory of Health and Environment, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, ENEA, Rome, Italy; 2Laboratory of Biotechnology, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, ENEA, Rome, Italy; 3Laboratory of Biomedical Technologies, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, ENEA, Rome, ItalyCorrespondence: Caterina Arcangeli; Mariateresa MancusoENEA, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Casaccia Research Centre, Via Anguillarese 301, Rome 00123, ItalyTel +39 06 3048 6898/4993Fax +39 06 3048 6559/3644Email [email protected]; [email protected]: The new frontier of tumor diagnosis and treatment relies on the development of delivery strategies capable of allowing the specific targeting of the diagnostic agents/chemotherapeutics, avoiding side effects. In the case of brain tumors, achieving this goal is made more difficult by the presence of the blood–brain barrier (BBB). Peptides have been revealed as excellent candidates for both BBB crossing and specific cancer homing. Nanoparticles (NPs), functionalized with BBB crossing and tumor homing (TH) peptides, are emerging as smart theranostic systems. However, there is still poor knowledge concerning the molecular structure and dynamical properties of these peptides, essential requirements for a suitable functionalization of the delivery systems themselves.Methods: In this work, by means of molecular dynamics (MD) simulations, we have extensively characterized the structural and dynamical behavior of several peptides, known to be endowed of BBB crossing and TH properties.Results: The simulations point out that, on the basis of their conformational dynamics, the peptides can be classified in two main groups: 1) peptides assuming a specific structural conformation, a feature that could be important for interacting with the molecular target but that may limit their use as functionalizing molecules and 2) highly flexible peptides whose interaction with the target may be independent of a particular structural conformation and that may represent good candidates for the functionalization of theranostic NP-based platforms.Discussion: Such findings may be useful for the de novo designing of NP-based delivery systems.Keywords: conformational flexibility, free energy landscapes, essential dynamics, peptides, brain, theranostic platform
