Impact of material characteristics on nanoparticle penetration and retention in thrombi: implications for thrombolysis

Ischemic cardiovascular disease is the leading cause of death worldwide and is primarily attributed to blood vessel occlusion caused by thrombi. While current treatments and research focus on overall thrombolytic activity, they often overlook the distribution of therapeutic agents or drug-loaded nanomaterials within the thrombus. This study is the first to systematically investigate how the material, size, shape, and charge of nanoparticles affect their ability to penetrate and distribute within a thrombus. The ultimate goal is to guide the development of more efficient thrombolytic nanomaterials. Recently, various metal (e.g. gold and silver) and metal oxide nanomaterials have been developed for thrombolysis and molecular imaging of thrombi. Based on this, we employed gold and silver nanoparticles in our study. Nanoparticles ranging from 10 to 200 nm in size, with both positive and negative surface charges, and in spherical and rod-shaped forms, were evaluated using two-photon microscopy, loop-based diffusion, and both static and dynamic microchannel thrombus models. It was found that the physicochemical characteristics of nanoparticles strongly influence their ability to penetrate and accumulate within the thrombus. In particular, the larger the particle size, the lower the penetration and the higher the retention. Negative surface charge and silver materials favour penetration of the particles compared to positively charged or gold particles, respectively. Particle shape is also an influence factor, where a rod shape reduces penetration and increases retention. These findings provide valuable insights for designing future diagnostic and therapeutic nanoparticles.