Liposome Imaging in Optically Cleared Tissues

3D microscopy of liposomes is currently challenging because it requires processing that removes lipids and makes tissues transparent. We developed a tag, termed REMNANT, for the 3D imaging of organic materials in biological tissues. We demonstrate the utility of this tag for the 3D mapping of liposomes in intact tissues. We also show the tag is able to monitor the release of entrapped therapeutic agents. We found that liposomes release their cargo >100-fold faster in tissues than in conventional in vitro assays. This allowed us to design a liposomal formulation with enhanced ability to kill tumour associated macrophages. Our development opens up new opportunities for studying the chemical properties and pharmacodynamics of administered organic materials in intact biological environment. This provides insight into the in vivo behavior of degradable materials, where the newly discovered information can guide the engineering of the next generation of imaging and therapeutic agents.