Abstract
The nanomedicine field continues to gain momentum, with several groundbreaking clinical trials underway. However, despite the promise of advanced antifouling nanoparticles incorporating poly(ethylene glycol)-a key component in the development of COVID-19 vaccines-the clinical translation of nanomedicine remains limited. This is primarily due to the relatively low delivery efficacy, with passive targeting relying on the enhanced permeability and retention effect, and active targeting leading to only modest improvements in target tissue accumulation. Improving the targeting, biocompatibility, and functionality of nanoparticles has the potential to create more effective, personalized, and minimally invasive therapies. This review aims to highlight the rise of a previously unidentified order of immune-minded nanomaterials and explores how mechanobiological principles and biomechanical nanotools are revolutionizing our understanding of nano-bio interactions in relation to disease. By considering mechanical properties such as stiffness, surface topology, and behavior under physiological flow conditions, researchers can better engineer nanoparticles for improved therapeutic outcomes.