Abstract: Virus-like particles (VLPs) are widely studied in bio-related applications, such as drug-and gene-delivery and disease diagnosis. The synthetic VLPs display excellent performance comparable to the natural virus and avoid the risk of using virus-generated particles such as virus capsids. However, most researches for preparing VLPs concern on mimicking the size and shape of the natural virus. Few work focuses on the surface nanostructure which is a key structure feature of the natural virus. As a matter of fact, the ordered surface nanostructure of the virus endows their superior cellular internalization capacity. Therefore, it is an urgent topic to construct VLPs with ordered surface nanostructures and study their cellular internalization behavior. In the past decade, Prof. Chunhua Cai and co-workers from East China University of Science and Technology have made significant contributions to the fabrication of polypeptide-based VLPs through a solution self-assembly approach. They found that polypeptide block copolymer/homopolymer mixtures were capable of self-assembling into hierarchical aggregates such as superhelices and woolballs. In these hierarchical aggregates, the homopolymers formed cylindrical or spherical inner core acting as templates and block copolymers self-assembled on the surface of the homopolymer templates into various nanostructures. These hierarchical aggregates mimicked the essential structure of natural virus, which contained a DNA or RNA core and a polypeptide capsid with ordered surface nanostructures. Furthermore, the cellular internalization behavior of these polypeptide VLPs was investigated, which indicated that these VLPs possessed excellent internalization efficiency, and their physical feature exerted significant effect on the internalization behavior. The results provided valuable information and guidance for controlling the structure and function of VLPs and could promote application of the VLPs in biomedicine.