Posted by Pancreatic cancer is resistant not only to chemotherapy but also to immunotherapy; therefore, identifying strategic alternatives is still necessary. Recently, the inducible T-cell co-stimulator (ICOS)/ICOS ligand (ICOSL) signaling has emerged as an interesting immunomodulatory pathway with anti-invasion activity. Interestingly, nanoparticle-based drug delivery platforms are a very promising tool since it is possible to combine chemotherapy and immunotherapy. Here, β-cyclodextrin-based nanosponges (NS) loaded with GEM and functionalized with ICOS-Fc (ICOS-Fc-NS-GEM) were evaluated as an innovative combination therapy, potentially suitable to overcome drug resistance in pancreatic cancer. NS-GEM affected viability, proliferation, and invasion in the 2D and 3D cultures of pancreatic cancer cells. Moreover, the combined formulation ICOS-Fc-NS-GEM showed an enhancement of anti-invasion properties. The MULTI-ORGAN single flow device (MIVO®) technology was exploited to confirm the anti-invasion effect, raising the system’s complexity and achieving evidence closer to the in vivo scenario.
Monica Argenziano, Chiara Monge, Anna Scomparin, Francesco Trotta, Valentina Boscaro, Ian Stoppa, Umberto Dianzani, Stefania Pizzimenti, Roberta Cavalli, Chiara Dianzani (2025) Gemcitabine-loaded ICOS-Fc decorated nanosponges: A new chemo immunotherapy combination against pancreatic cancer.
International Journal of Pharmaceutics 125869. https://doi.org/10.1016/j.ijpharm.2025.125869