Nanomaterial-based drug delivery: overcoming current treatment barriers of pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, with a five-year survival rate below 5% and an increasing global mortality rate. The high lethality of PDAC is attributed to late-stage diagnosis and resistance to conventional treatments. A major driver of this therapeutic failure is the unique tumor microenvironment, characterized by a dense, fibrous stroma composed of cancer-associated fibroblasts, pancreatic stellate cells, and an overabundance of extracellular matrix. This stromal fortress prevents most of the administered drugs from reaching the targeted tumor site, thus reducing the therapeutic efficacy. Nanomaterials have drawn more attention in recent decades for PDAC diagnosis and treatment. Nanomaterials offer sophisticated advantages, such as preventing enzymatic degradation, increasing solubility, and precise targeting. Despite challenges regarding long-term toxicity and clinical translation remaining, integrated multifunctional nanomaterials represent a promising opportunity to overcome the obstacles related to PDAC. This review examines the present conditions and limitations of PDAC treatment and highlights the transformative potential of nanomaterial-based drug delivery systems for the precision delivery of chemotherapeutic agents and combinational alternatives that address the chemoresistance associated with PDAC.