We investigated the comparative effects of Cu 15 mol % doped $TiO_2$ (anatase crystal phase, 20 ppt) nanoparticles and pure $TiO_2$ (anatase crystal phase, 20 ppt) nanoparticles on cellular toxicity, penetration, and gene expression in zebrafish embryogenesis. HR-TEM analysis observed that pure $TiO_2$ particles were in the form of small balls (<10 nm), while Cu-doped (15 mol %) $TiO_2$ particles were large (20-70 nm) squares and balls. Both Cu/$TiO_2$ and pure $TiO_2$ nanoparticles penetrated into cells. Cu/$TiO_2$ nanoparticles penetrated into the yolk sac epithelial cells of zebrafish larvae as aggregated particles. Mitochondria in embryos exposed to Cu/$TiO_2$ nanoparticles were damaged and did not contain cristae. In microarray analysis, several genes involved in apoptosis and endocytosis regulation were differentially expressed according to nanoparticle type. Bcl2 gene expression was significantly upregulated in embryos exposed to both Cu/$TiO_2$ and pure $TiO_2$ in comparison to the control group. Cu/$TiO_2$ nanoparticles caused more damage than pure $TiO_2$ nanoparticles and resulted in apoptosis during zebrafish development.