Deformable discoidal polymeric nanoconstructs: Design principles, therapeutic applications, and translational perspectives

Abstract Deformable Discoidal Polymeric Nanoconstructs (DPN) represent a biomimetic drug-delivery platform designed to overcome the limitations of conventional spherical nanoparticles. Their discoidal geometry, tunable deformability, and PLGA/PEG-based composition promote vascular margination, reduce phagocytic sequestration, prolong circulation, and enhance accumulation at pathological sites. This review highlights the design principles, fabrication strategies, therapeutic applications, and translational potential of DPN. In oncology, DPN have been engineered to improve the loading and sustained release of docetaxel through multi-passage fabrication, prodrug conjugation, and hierarchical micro-combinatorial hydrogel particles (µCGP). These discoidal particles enhanced therapeutic efficacy in preclinical models of triple-negative breast cancer, glioblastoma, and lung metastases. Beyond cancer, surface-functionalized DPN carrying tissue plasminogen activator improved clot targeting and thrombolysis while limiting neurological toxicity in ischemic stroke models. Overall, DPN integrate geometry, mechanics, and surface functionality to achieve vascular confinement, targeted delivery, and improved safety. Their modular design, biocompatible materials, and favorable preclinical performance support further development as versatile platforms for cancer therapy, metastatic disease, and thrombotic disorders.