Tailoring Virus-Inspired Nanoparticles for Advanced Drug and Gene Delivery

Viruses, as naturally evolved gene delivery systems, exhibit exceptional efficiency in overcoming biological barriers, targeting specific cells, and inducing robust immune responses. Inspired by these characteristics, virus-mimicking nanocarriers have become a promising strategy for enhancing drug and gene delivery. This review provides a detailed exploration of virus-inspired nanodelivery systems, with particular emphasis on their structural and functional biomimetic properties. We first focus on natural viral delivery platforms, such as viral nanoparticles and virus-like particles. Then, we discuss the application of biomimetic strategies that mimic viral morphology and topological structure in overcoming multiple physiological barriers in the body. Particularly, we examine bioinspired strategies that mimic key viral infection functions, including overcoming physiological barriers, cell adhesion and surface recognition, membrane fusion and cellular internalization, environmental perception and endosomal escape, intracellular trafficking and organelle targeting, and immune modulation. Additionally, we highlight the integration of intelligent strategies to optimize delivery efficiency. Finally, we discuss the current challenges and future opportunities in the field, aiming to advance virus-inspired nanomedicine toward clinical applications. TOC:Overview of the classification of virus-mimicking nanocarrier systems. Created in BioRender. Li, H. (2026) https://BioRender.com/e64s547 . (1) Virus-based Nano-DDS ( e.g. VNPs, VLPs and nanocarriers which incorporate viral active components to enhance delivery efficiency). (2) Structure-biomimetic strategies ( e.g. size and morphology optimization, viral capsids-mimicking spiky surface topography and core-shell structures). (3) Functional biomimetic strategies ( e.g. cell surface receptor recognition, membrane fusion, intracellular transport, signal transduction and immune activation). (4) The center of the figure illustrates the ability of virus-mimicking Nano-DDS to overcome multiple biological barriers.