Abstract
Polyamidoamine (PAMAM) dendrimers, with their unique structural versatility and tunable surface functionalities, have emerged as promising nanomaterials for a wide range of biomedical applications. However, their in vivo use raises concerns, as unintended interactions between dendrimers and blood components could disrupt the delicate hemostatic balance and lead to serious complications like bleeding or thrombosis. In this study, we explored the impact of low-generation PAMAM dendrimers on the kinetics of fibrin clot formation, along with their influence on the structure, properties, and resistance to lysis of the resulting clots. For this purpose, we employed a multilevel characterization approach using purified fibrinogen, human plasma, and whole blood to assess the effects of four dendrimer types: G2-NH(2), G4-NH(2), G3.5-COOH, and G4-OH. Among the main findings, both G2-NH(2) and G4-NH(2) significantly impaired thrombin generation and delayed clot formation, with G4-NH(2) also promoting fibrin aggregation, increasing clot permeability, and accelerating clot lysis. When present at high concentrations, G4-OH also affected critical clotting parameters, delaying thrombin generation and prolonging clotting time. Notably, the prolongation of clotting time by G4-OH was evident in both human plasma and whole blood. Interestingly, G3.5-COOH showed potential as a safer option since it induced minimal alterations across most tested metrics. These results will be important for guiding the rational design of dendrimers and identifying safe concentrations for future clinical applications.