Abstract
The dynamic change of cell-surface glycans is involved in diverse biological and pathological events such as oncogenesis and metastasis. Despite tremendous efforts, it remains a great challenge to selectively distinguish and label glycans of different cancer cells or cancer subtypes. Inspired by biomimetic cell membrane-coating technology, herein, we construct pH-responsive azidosugar liposomes camouflaged with natural cancer-cell membrane for tumor cell-selective glycan engineering. With cancer cell-membrane camouflage, the biomimetic liposomes can prevent protein corona formation and evade phagocytosis of macrophages, facilitating metabolic glycans labeling in vivo. More importantly, due to multiple membrane receptors, the biomimetic liposomes have prominent cell selectivity to homotypic cancer cells, showing higher glycan-labeling efficacy than a single-ligand targeting strategy. Further in vitro and in vivo experiments indicate that cancer cell membrane-camouflaged azidosugar liposomes not only realize cell-selective glycan imaging of different cancer cells and triple-negative breast cancer subtypes but also do well in labeling metastatic tumors. Meanwhile, the strategy is also applicable to the use of tumor tissue-derived cell membranes, which shows the prospect for individual diagnosis and treatment. This work may pave a way for efficient cancer cell-selective engineering and visualization of glycans in vivo.