Glioma features high fatality rate and short survival time of patients due to its fast growth speed and high invasiveness, hence timely treatment of early‐stage glioma is extremely important. However, the blood brain barrier (BBB) severely prevents therapeutic agents from entering the brain; meanwhile, the non‐targeted distribution of agents always causes side effects to vulnerable cerebral tissues. Therefore, delivery systems that possess both BBB penetrability and precise glioma targeting ability are keenly desired. We herein proposed a hybrid cell membrane (HM) camouflage strategy to construct therapeutic nanocomposites, in which HM consisting of brain metastatic breast cancer cell membrane and glioma cell membrane was prepared with a simple membrane fusion pathway. By coating HM onto drug‐loaded nanoparticles, the as‐obtained biomimetic therapeutic agent (termed HMGINPs) inherited satisfying BBB penetrability and homologous glioma targeting ability simultaneously from the two source cells. HMGINPs exhibited good biocompatibility and superior therapeutic efficacy towards early‐stage glioma.

Glioma features high fatality rate and short survival time of patients due to its fast growth speed and high invasiveness, hence timely treatment of early‐stage glioma is extremely important. However, the blood brain barrier (BBB) severely prevents therapeutic agents from entering the brain; meanwhile, the non‐targeted distribution of agents always causes side effects to vulnerable cerebral tissues. Therefore, delivery systems that possess both BBB penetrability and precise glioma targeting ability are keenly desired. We herein proposed a hybrid cell membrane (HM) camouflage strategy to construct therapeutic nanocomposites, in which HM consisting of brain metastatic breast cancer cell membrane and glioma cell membrane was prepared with a simple membrane fusion pathway. By coating HM onto drug‐loaded nanoparticles, the as‐obtained biomimetic therapeutic agent (termed HMGINPs) inherited satisfying BBB penetrability and homologous glioma targeting ability simultaneously from the two source cells. HMGINPs exhibited good biocompatibility and superior therapeutic efficacy towards early‐stage glioma.

The changes of blood–brain barrier (BBB) permeability need to be sensitively reported when purposefully regulating the BBB or during some brain diseases. Currently available techniques for assessment of BBB integrity all suffer from limited sensitivity and only report serious BBB damage. Here, a targeted activatable nanoprobe is created to monitor subtle changes of BBB permeability by detecting the expression levels of BBB permeability-related miRNA (miRNA-155) in brain microvessel endothelial cells (BMECs). The probe is fabricated by coating the BMEC membrane on calcium phosphate (CaP)-mineralized metal-organic framework (MOF) nanoparticles loaded with hybridization chain reaction (HCR) probes. The coating of the BMEC membrane endows the nanoprobe with homologous targeting ability to BBB, and HCR probes released and escaped from lysosomes can be specifically lightened by miRNA-155. The activatable nanoprobe is able to monitor BBB permeability in inflammatory and AD mice. This work provides a new idea for highly sensitive evaluation of the BBB permeability, which has guiding significance in regulating BBB and formulating targeted therapeutic strategies.