Mihai Lomora

Mechanoresponsive drug delivery systems (DDS) have emerged as promising candidates to improve the current effectiveness and lower the side effects typically associated with direct drug administration in the context of vascular diseases. Despite tremendous research efforts to date, designing drug delivery systems able to respond to mechanical stimuli to potentially treat these diseases is still in its infancy. By understanding relevant biological forces emerging in healthy and pathological vascular endothelium, it is believed that better‐informed design strategies can be deduced for the fabrication of simple‐to‐complex macromolecular assemblies capable of sensing mechanical forces. These responsive systems are discussed through insights into essential parameter design (composition, size, shape, and aggregation state) , as well as their functionalization with (macro)molecules that are intrinsically mechanoresponsive (e.g., mechanosensitive ion channels and mechanophores). Mechanical forces, including the pathological shear stress and exogenous stimuli (e.g., ultrasound, magnetic fields), used for the activation of mechanoresponsive DDS are also introduced, followed by in vitro and in vivo experimental models used to investigate and validate such novel therapies. Overall, this review aims to propose a fresh perspective through identified challenges and proposed solutions that could be of benefit for the further development of this exciting field.