Ultrasmall anti-HER2 fluorescent core–shell silica nanoparticles not only showed great enhancement on accumulation and retention at the target site but also improved target tissue penetration and diffusion, likely associated with their ultrasmall particle size (< 10 nm), overcoming the limitation of nanoparticle distribution in perivascular tumor cells commonly observed for larger nanoparticles. This evidence concerns the gene ERBB2 and neoplasm.