Background:Glioma as a highly lethal tumor is difficult to treat since the blood-brain barrier (BBB) restricts drug delivery into the brain. It remains a huge need for developing strategies allowing drug passage across the BBB with high efficacy.Methods:Herein, we engineered drug-loaded apoptotic bodies (Abs) loaded with doxorubicin (Dox) and indocyanine green (ICG) to cross the BBB for the treatment of glioma. The confocal laser scanning microscopy was used to characterize the structure and evaluate the hitchhiking effect of the Abs. Thein vivoBBB-crossing ability and photothermal-chemotherapeutic effect of the drug-loaded Abs were investigated in mice orthotopic glioma model.Results:Engineered Abs loaded with Dox and ICG were successfully prepared. The Abs were phagocytized by macrophages, actively penetrate the BBBin vitroandin vivoutilizing the hitchhiking effect. The wholein vivoprocess was visualized by near-infrared fluorescence signal with a signal-to-background ratio of 7 in a mouse model of orthotopic glioma. The engineered Abs achieved a combined photothermal-chemotherapeutic effect, leading to a median survival time of 33 days in glioma-bearing mice compared to 22 days in the control group.Conclusions:This study presents engineered drug carriers with the ability to hitchhike across the BBB, providing new opportunities for the treatment of glioma.