Pancreatic cancer is one of the deadliest cancers with an increasing incidence due to a lack of early-stage diagnostics and effective treatment [1]. The RAS/RAF/ MAPK/CDK4 pathway is frequently dysregulated in pancreatic cancer and CDK4 constitutes an attractive target since several drugs have been approved by the FDA to inhibit its activity: Abemaciclib, Ribociclib and Palbociclib [2,3] (Figure 1) However these inhibitors are not efficient in monotherapy and have only been approved for breast cancer. In order to propose an efficient therapeutic strategy to target CDK4 in pancreatic cancer, we propose to deliver Abemaciclib using carbon nanotubes.
Carbon nanotubes are promising materials for nanomedicine applications and especially for drug delivery. [4] In this project, we adsorb Abemaciclib onto single-walled carbon nanotubes (SWNT) for delivery of the drug into pancreatic cancer cells. In order to study adsorption, we investigate the changes in the optical signatures of SWNTs in the near-infrared (NIR) by coupling NIR absorption, photoluminescence and Raman spectroscopies. [5] Typical kinetic spectroscopic results, assigned to the adsorption of Abemaciclib on SWNT, dispersed in water using carbomethylcellulose (CMC), are presented in Figure 2. We discuss the results in terms of changes of the dielectric environment of the nanotubes, leading to modulation of their excitonic and optical properties. We have further investigated the inhibitory potential of SWNT-Abemaciclib on proliferation of PANC1 cells compared to Abemaciclib alone and have determined the toxic threshold of SWNT dispersed in CMC.