An Ultrastable Virus‐Like Particle with a Carbon Dot Core and Expanded Sequence Plasticity

Abstract Ordered bio‐inorganic hybridization has evolved for the generation of high‐performance materials in living organisms and inspires novel strategies to design artificial hybrid materials. Virus‐like particles (VLPs) are attracting extensive interest as self‐assembling systems and platforms in the fields of biotechnology and nanotechnology. However, as soft nanomaterials, their structural stability remains a general and fundamental problem in various applications. Here, an ultrastable VLP assembled from the major capsid protein (VP1) of simian virus 40 is reported, which contains a carbon dot (C‐dot) core. Co‐assembly of VP1 with C‐dots led to homogeneous T = 1 VLPs with a fourfold increase in VLP yields. The resultant hybrid VLPs showed markedly enhanced structural stability and sequence plasticity. C‐dots and a polyhistidine tag fused to the inner‐protruding N‐terminus of VP1 contributed synergistically to these enhancements, where extensive and strong noncovalent interactions on the C‐dot/VP1 interfaces are responsible according to cryo‐EM 3D reconstruction, molecular simulation, and affinity measurements. C‐dot‐enhanced ultrastable VLPs can serve as a new platform, enabling the fabrication of new architectures for bioimaging, theranostics, nanovaccines, etc. The hybridization strategy is simple and can easily be extended to other VLPs and protein nanoparticle systems.