Virus-Like Particle Nanocarriers for Precision Chemotherapy

Virus-like particles (VLPs) are self-assembling protein nanostructures that replicate the structural precision of viral capsids while lacking genetic material, rendering them inherently safe and highly modular biomaterials. Their genetically encoded architecture enables precise control over size, symmetry, mechanical stability, surface topology, and internal cavity volume, positioning VLPs as programmable protein-based nanocarriers for chemotherapeutic delivery. Recent advances in capsid engineering, biorthogonal conjugation, and template-guided assembly have enabled fine tuning of cargo loading, targeting ligand display, and stimuli-responsive drug release. Unlike many synthetic nanocarriers, VLPs offer atomically defined structure–function relationships, allowing rational modulation of biodistribution, cellular uptake, immune recognition, and therapeutic performance. This review examines VLPs as engineered protein biomaterials for precision chemotherapy, highlighting strategies for internal cargo integration, interfacial surface modification, mechanical reinforcement, and microenvironment-triggered release. Here we discuss how physicochemical parameters govern biological interactions and translational feasibility. Clinical progress underscores both the promise and remaining challenges of scalable manufacturing and immune modulation. By integrating biomaterials design principles with translational constraints, this review outlines a framework for the rational development of clinically viable VLP-based chemotherapeutic systems.