Over past three decades,the approaches to targeting nanomaterials in vivo have been intensely explored.However,the level of antitumor agent in tumor sites is still low.On the other hand,after extravasation from tumor vessels,nanocarriers are mainly limited to the very adjacent regions,leaving large tumor areas untouched by the therapeutic agents.Here we report an improvement in nanoparticle design to enhance drug accumulation and penetration at tumor site.We prepared a series of polymer nanoparticles with different sizes and surface chemistry.We demonstrated that the drug accumulation and particle residence time at tumor site can be significantly improved by incorporating targeting group into the nanoparticles,optimizing particle size and decorating particle surface.