Programmable Poly-Lactic-Co-Glycolic Acid Nanocarriers for Precision Therapy of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, characterized by late-stage diagnosis, dense desmoplastic stroma, rapid metastatic progression, and poor responsiveness to conventional chemotherapy. Consequently, the development of effective drug delivery strategies capable of overcoming stromal and resistance barriers remains an urgent clinical priority. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles have emerged as a versatile biomaterials platform for improving therapeutic outcomes through enhanced drug solubility, sustained release, and favorable pharmacokinetics. This review critically examines recent advances in the rational design and functionalization of PLGA-based nanocarriers for PDAC therapy, with particular emphasis on tumor-targeted delivery, stromal modulation, and strategies to overcome multidrug resistance. Surface engineering approaches, including ligand conjugation and stimuli-responsive systems, have shown considerable promise in enhancing intratumoral penetration and therapeutic efficacy. In addition, advanced nanoscale analytical and interfacial characterization techniques such as dynamic light scattering, electron microscopy, and zeta potential analysis provide important mechanistic insights into particle stability, cellular interactions, and drug-polymer dynamics, thereby guiding formulation optimization. Collectively, current evidence highlights the strong translational potential of PLGA nanocarriers in precision oncology for PDAC. Continued integration of biomaterials engineering with disease-specific targeting and rigorous physicochemical characterization will be essential to accelerate clinical development and improve patient outcomes.