Controlled delivery of a protein tyrosine phosphatase inhibitor, SHP099, using cyclodextrin-mediated host-guest interactions in polyelectrolyte multilayer films for cancer therapy

The Src homology 2 domain containing protein tyrosine phosphatase-2 (SHP2) is a key enzyme in pathways regulating tumor growth signaling, and recently gained interest as a promising anticancer drug target. Many SHP2 inhibitors are currently under development, including SHP099, which has shown potent anticancer activity at low concentrations in vivo. In this work, we developed multilayer coatings for localized delivery of SHP099 to improve upon current cancer therapies. Layer-by-layer self-assembly was used to develop films composed of chitosan and poly-carboxymethyl-beta-cyclodextrin (P beta CD) for the delivery of SHP099. SHP099 was successfully loaded into multilayer films via host-guest interactions with P beta CD. Nuclear magnetic resonance spectroscopy confirmed the occurrence of this supramolecular assembly by identifying the interaction of specific terminal SHP099 protons with the protons of the CD. SHP099 release from assembled films was detected over 96 hours, and was found to inhibit colony formation of human breast adenocarcinoma cells in vitro. These multilayer films have the potential to be used in a range of anticancer applications and overcome common complications of systemic chemotherapeutic administration, while maximizing SHP099 efficacy.