The EPR effect works primarily through two mechanisms:
1. Enhanced Permeability: Tumor blood vessels are often irregular, poorly aligned, and have wide fenestrations (gaps) between endothelial cells. These gaps can range from 100 to 800 nanometers, allowing nanoparticles to pass through more easily compared to normal tissues.
2. Reduced Retention: Tumors lack an efficient lymphatic drainage system, leading to the accumulation of nanoparticles in the tumor interstitium. This prolonged retention enhances the concentration of therapeutic agents within the tumor, improving the efficacy of the treatment.