Targeting the PI3K/Akt/mTOR pathway with nanotechnology: A novel therapeutic strategy for gastrointestinal cancers.

Gastrointestinal cancers are among the most common and deadly malignancies, with millions of fatalities annually. The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling cascade is integral to the advancement, survival, and therapeutic resistance associated with gastrointestinal (GI) malignancies. Despite advancements in chemotherapy, challenges like drug resistance and side effects highlight the need for innovative treatments. Nanotechnology offers a promising solution by improving the precision and efficacy of therapies targeting this pathway while minimizing adverse effects. This review discusses the PI3K/Akt/mTOR pathway's role in gastrointestinal cancers and explores nanoparticle-based therapeutic approaches. Nanoparticles are classified into metal-based (e.g., selenium, gold, silver, iron oxide, and zinc oxide nanoparticles), lipid-based (e.g., liposomes, micelles, and solid lipid nanoparticles), and polymeric nanoparticles (e.g., dendrimers, nanospheres). Recent research on these approaches and ultra-small nanoparticles and superparticles is discussed along with their importance. This review also addresses the challenges, limitations, and prospects of the field.