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- Therapeutic targeting of CDK4 kinase in pancreatic cancerusing functionalized single-walled carbon nanotubes hal link

Auteur(s): Chavignon L.(Corresp.), Blanc C., Morris May, Anglaret E.

(Affiches/Poster) Chemontubes 2022 (San Sebastian, ES), 2022-04-24


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Résumé:

Pancreatic cancer is one of the deadliest cancers with an increasing incidence due to a lack ofearly-stage diagnostics and effective treatment [1]. The RAS/RAF/ MAPK/CDK4 pathway is frequentlydysregulated in pancreatic cancer and CDK4 constitutes an attractive target since several drugs havebeen approved by the FDA to inhibit its activity: Abemaciclib, Ribociclib and Palbociclib [2,3] (Figure1) However these inhibitors are not efficient in monotherapy and have only been approved for breastcancer. In order to propose an efficient therapeutic strategy to target CDK4 in pancreatic cancer, wepropose to deliver Abemaciclib using carbon nanotubes.
Carbon nanotubes are promising materials for nanomedicine applications and especially fordrug 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 thechanges 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 tothe adsorption of Abemaciclib on SWNT, dispersed in water using carbomethylcellulose (CMC), arepresented in Figure 2. We discuss the results in terms of changes of the dielectric environment of thenanotubes, leading to modulation of their excitonic and optical properties. We have furtherinvestigated the inhibitory potential of SWNT-Abemaciclib on proliferation of PANC1 cells comparedto Abemaciclib alone and have determined the toxicthreshold of SWNT dispersed in CMC.