Motivation: Biomimetic Nanocarriers for Enhanced Drug Diffusion in Prostate Tumors with a High Level of Hyaluronan • Prostate cancer is the most common cancer in men and is the second highest leading cause of cancer related death in men. • Currently available treatment methods are very expensive, invasive, not effective enough and have many side effects. • Nanocarriers can alter pharmacokinetics and toxicity of encapsulated drugs to improve efficacy and reduce side effects. • Diffusion of nanoparticles and drug molecules are significantly reduced in cancers with a high level hyaluronan. Objective: Fabricate biomimetic composite nanoparticles with extra cellular matrix degrading enzymes on surfaces to achieve high tumortargeting capability and superior diffusion within tumors compared to particles without ECMDEs. Approach: Conclusions: Contact: RBC-PLGA-NPs with HAase on surfaces were successfully fabricated. Hao Cheng, PhD Assistant Professor Materials Science & Engineering email@example.com (215) 895-1640 HAase on surfaces of RBC-PLGA-NPs enhanced nanoparticle penetration and diffusion into the pericellular HA layer of PC3 cells. Fabricated biomimetic nanoparticles with HAase on surfaces can be used as drug delivery devices for cancers with a high level hyaluronan.