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Theranostics 2023; 13(9):2966-2978. doi:10.7150/thno.80632 This issue Cite

Research Paper

Engineered apoptotic bodies hitchhiking across the blood-brain barrier achieved a combined photothermal-chemotherapeutic effect against glioma

Yu Liu^1,2,4#, Dehong Hu^1#, Duyang Gao^1✉, Ping Gong³, Hairong Zheng¹, Minjie Sun^2✉, Zonghai Sheng^1✉

1. Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P.R. China.
2. State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, P. R. China.
3. Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Bioactive Materials Engineering Lab for Medicine, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P. R. China.
4. Cancer Centre, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, P. R. China.
^# These authors contributed equally to this work.

✉ Corresponding authors: Email address: dy.gaoac.cn (D. Gao); msunedu.cn (M. Sun); zh.shengac.cn (Z. Sheng).

Abstract

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. The in vivo BBB-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 BBB in vitro and in vivo utilizing the hitchhiking effect. The whole in vivo process 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.

Keywords: Apoptotic bodies, Blood-brain barrier, Drug delivery, Glioma, Photothermal therapy

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