Biomimetic Nanocomposites Cloaked with Bioorthogonally Labeled Glioblastoma Cell Membrane for Targeted Multimodal Imaging of Brain Tumors

Brain tumor targeted delivery of diagnostic contrast agents has been an elusive goal due to the presence of the blood brain barrier (BBB) and the complex brain tumor microenvironment. Herein, an ingenious design of nanoscale contrast agents coated by bioorthogonally labeled brain tumor cell membrane for targeted diagnosis of glioblastoma through multiple complementary imaging modalities is presented. Taking advantage of bioorthogonal click reactions, an endothelial integrin receptor-targeting peptide cRGD is decorated onto the nanocomposite surface to act in synergy with brain tumor cell membrane to offer BBB-penetrating and homotypic targeting effect in the brain tumor microenvironment. Cellular and animal experimental results validate the superior targeting outcomes achieved by cRGD-labeled brain tumor cell membrane coating. This study offers an example of a surface modified cell membrane as a potential theranostic strategy to overcome the delivery barriers in brain tumors.