Objective

The intrinsic promiscuity of tyrosin kinase inhibitors (TKI) in the treatment of cancer requires new methods to systematically approach the elucidation of targets, as first step in the development of highly selective personalized therapies. This nanotechnology-based tool aims to offer the possibility to make the interrogation of the full proteome possible for a certain drug in a particular cell environment. The development and characterization of multifunctionalized polystyrene nanoparticles with drugs and fluorophores will be described. Moreover, the validation of this nanoprobe in vitro and in cellulo will be presented. The chemical conjugation of a fluorescent moiety to this nanoprobe allows tracking and co-localization of the nanoparticles inside the cells with target kinases. Furthermore, the presence of a solid nanoparticle core allows the isolation of high affinity targets for further analysis. This study represents the proof of concept for the development of a cell-permeable nanoprobe able to detect in-situ the targets of TKIs and appears as a suitable nanoprobe for chemical proteomics in target deconvolution.