Deformable Discoidal Polymeric Nanoconstructs for the Precise Delivery of Therapeutic and Imaging Agents.

Over the last 15 years, a plethora of materials and different formulations have been proposed for the realization of nanomedicines. Yet drug-loading efficiency, sequestration by phagocytic cells, and tumor accumulation are sub-optimal. This would imply that radically new design approaches are needed to propel the clinical integration of nanomedicines, overcoming well-accepted clichés. This work briefly reviews the use of deformable discoidal nanoconstructs as a novel delivery strategy for therapeutic and imaging agents. Inspired by blood cell behavior, these nanoconstructs are designed to efficiently navigate the circulatory system, minimize sequestration by phagocytic cells, and recognize the tortuous angiogenic microvasculature of neoplastic masses. This article discusses the notion of nanoparticle margination and vascular adhesion, as well as advantages associated with deformable particles. Finally, details on the synthesis, physico-chemical properties, and in vivo characterization of discoidal polymeric nanoconstructs are provided, with particular emphasis on their ability to independently control size, shape, surface properties, and mechanical stiffness. These nanoconstructs could help in gaining a deeper understanding of the mechanisms regulating the behavior of nanomedicines and identifying optimal delivery strategies for patient-specific therapeutic interventions.