Recent progress in gemcitabine-loaded nanoparticles for pancreatic cancer therapy: a review

The treatment of pancreatic cancer remains a formidable challenge. Despite recent advances in diagnostic techniques and therapeutic approaches, the overall five-year survival rate for patients with pancreatic cancer remains below 9%, reflecting a dismal prognosis. Currently, surgical resection is the only potentially curative option; however, only about 10% of patients are eligible for surgery at the time of diagnosis. For those with unresectable locally advanced or metastatic pancreatic cancer, chemotherapy remains the mainstay of treatment. In this context, gemcitabine (GEM), a conventional chemotherapeutic agent, holds significant clinical value due to its potent anti-pancreatic cancer activity. Nevertheless, its clinical application has long been hampered by limitations such as a short half-life, rapid metabolic degradation, poor tumor tissue penetration, and dose-dependent toxicity. Although conventional GEM-based nanoformulations have partially improved its pharmacokinetic properties, their therapeutic efficacy and safety still require further enhancement. In recent years, researchers have focused on developing novel nanodelivery systems aimed at overcoming the clinical limitations of GEM through innovative carrier designs and advanced delivery strategies. This review briefly introduces the mechanisms underlying gemcitabine resistance and systematically highlights recent advances in emerging nanoparticles loaded with GEM. Particular attention is given to functional nanocarriers for GEM monotherapy, self-assembled GEM prodrug nanostructures, and GEM-based combinational nanotherapies. Finally, this review discusses the current challenges and future opportunities for the clinical translation of these emerging nanoplatforms.