Fibrinolytic tissue plasminogen activator installed redox-active nanoparticles (t-PA@iRNP) for cancer therapy

Favorable blood flow within solid tumors has become the principal strategy for drug delivery. The use of thrombolytic drugs, such as tissue plasminogen activator (t-PA), in combination with other drugs or drug carriers may increase their therapeutic effect by increasing drug delivery near the solid tumor through fibrin degradation and blood flow restoration. We, therefore, designed t-PA-installed redox-active nanoparticles (t-PA@iRNP) to improve the perfusion of antioxidant nanoparticles in tumors, via fibrin degradation to decompress tumor vessels. Additionally, antioxidant iRNP was developed for tumor inhibition by reduction of critically elevated levels of reactive oxygen species (ROS) in tumors. The t-PA@iRNP, when administered to a colon cancer model, degraded the deposited fibrin and improved the iRNP and immune cells penetration in tumor tissues via the restored blood flow, thus more effectively inhibited tumor growth. The anti-tumor effect of iRNP was attributed to ROS-reduction mediated downregulation of crucial a transcriptional factor, NF-kappa B. Conclusively, this study provides a new strategy to enhance the delivery of nanotherapeutics into solid tumors.