Silk fibroin-coated nanoparticles for safe and efficient antithrombotic drug delivery

Long-term pharmacological intervention is essential for managing chronic diseases, yet continuous administration of antithrombotic agents often increases bleeding risk, posing a major clinical challenge. Here, we designed a multifunctional drug delivery platform composed of large-aperture mesoporous silica (Mas) coated with silk fibroin (SF) or sustained heparin sodium (HS) release. The well-defined mesoporous structure enables high drug loading, while the biocompatible SF coating regulates release kinetics, suppresses burst release, and prolongs therapeutic efficacy. This dual structural system enhances antithrombotic performance while mitigating hemorrhagic risk. In vitro studies demonstrated improved hemocompatibility and reduced cytotoxicity of SF-Mas/HS compared with free HS. In vivo thrombosis models further confirmed effective inhibition of thrombus formation without excessive bleeding. By integrating inorganic mesoporous carriers with natural protein coatings, SF-Mas/HS provides a safe and efficient strategy for long-term antithrombotic prevention, highlighting the potential of biomaterial-assisted delivery systems to balance efficacy and safety in chronic disease management.