Biofunctionalization of Silica Nanoparticles with Cell-Penetrating Pepties: Asorption Mechanism an Bining Energy Estimation

Nanoparticles represent one of the most promising materials as they have foun application in bionanotechnology for enhance imaging, iagnosis, an treatment of several iseases. Silica coating is wiely use to improve colloial stability an the bining affinity of nanoparticles for various organic molecules, such as cell-penetrating pepties (CPPs). The functionalization of the silica coating by CPPs is very promising, since it enhances the uptake of the nanoparticles ue to the intrinsic ability of the CPPs to cross the cellular membrane. However, molecular level phenomena characterizing the CPPs interaction with silica-coate nanoparticles are not clarifie yet. In this work, classical molecular ynamics has been use to she light on the asorption mechanism of several CPPs onto silica surfaces, in orer to highlight the influence of the surface ionization's state on the asorption mechanism. Our ata highlight how the cationic pepties strongly interact with the anionic silica surfaces by H-bon formation between charge resiues an the negatively charge siloxie groups, as well as ion pairing between the surfaces an the N-termini resiues. Moreover, thanks to metaynamics simulations the CPP-silica bining affinity has been quantifie. The free energy profile escription allows proviing insight into the relationship between ionization of silica nanoparticles an bining selectivity/specificity to CPP.