Breaking barriers: nano-boosted drug delivery systems in overcoming the defenses of pancreatic cancer

Pancreatic cancer (PC) remains a highly lethal malignancy presenting formidable therapeutic challenges, primarily attributable to the substantial barriers posed by its dense desmoplastic stroma, profoundly immunosuppressive microenvironment, and poor drug bioavailability. Nanotechnology offers an effective strategy to enhance therapeutic efficacy through improved targeting, optimized pharmacokinetics, enhanced tissue penetration, increased biosafety, and high clinical translational potential. Consequently, this nanotechnology-based platform has been extensively investigated over the past decade for treating PC. This review examines a comprehensive overview of nanoparticle-mediated delivery systems for targeted PC therapy, critically evaluating recent developments and ongoing hurdles along the bench-to-bedside pathway. We discuss applications across chemotherapy, immunotherapy, gene therapy, and other modalities employed as monotherapies or combination regimens.