Micro/nanoparticles have been thought to affect cardiovascular system and trigger cardiovascular disorders.Nanoparticles prepared from PEG-b-PCL,a widely studied biodegradable copolymer,are promising carriers for the drug delivery systems.However,it remains unknown whether polymeric PEG-b-PCL nano-micelles have any potential complications on cardiovascular system.In this study,we used zebrafish as a model to in vivo evaluate PEG-b-PCL effects on cardiovascular development.PEG-b-PCL nano-micelles caused embryo mortality,reduced hatching rate as well as embryonic and larval malformations in a dose-dependent manner.To determine PEG-b-PCL effects on embryonic angiogenesis,a critical process in zebrafish cardiovascular development,we used fluorescent stereomicroscopy to measure growth of intersegmental vessels and caudal vessels in flk1-GFP transgenic zebrafish embryos.We also used quantitative real-time PCR(qPCR)and in situ whole-mount hybridization to analyze expression of angiogenic factor,flk1.PEG-b-PCL decreased growth of intersegmental vessels and caudal vessels,as well as reduced flk1 expression in a concentration-dependent manner.Parallel to the inhibitory effects on angiogenesis,qPCR and TUNEL analysis showed that PEG-b-PCL exposure up-regulated p53 pro-apoptotic pathway and induced cellular apoptosis in angiogenic regions.We further showed that inhibiting p53 activity,either by pharmacological inhibitor or siRNA knockdown could abrogate the apoptosis and angiogenic defects caused by PEG-PCL nano-micelles,indicating that PEG-PCL nano-micelles inhibit angiogenesis by activating p53-mediated apoptosis.Our study indicates that polymeric PEG-PCL nano-micelles may pose potential hazards to cardiovascular system.