Virus-like particles (VLPs) are stable protein cages derived from virus coats. They have been used extensively as biomolecular platforms, e.g., nano carriers or vaccines, but a convenient in situ technique is lacking for tracking functional status. Here, we present a simple way to monitor disassembly of F-19-labeled VLPs derived from bacteriophage Q beta by F-19 NMR Analysis of resonances, under a range of conditions, allowed determination not only of the particle as fully assembled but also as disassembled, as well as detection of a degraded state upon digestion by cells. This in turn allowed mutational redesign of disassembly and testing in both bacterial and mammalian systems as a strategy for the creation of putative, targeted-VLP delivery systems.