Aptamer-Modified Erythrocyte Membrane-Coated pH-Sensitive Nanoparticles for c-Met-Targeted Therapy of Glioblastoma Multiforme
Xianping Liu,
Yixin Chen,
Daoying Geng,
Haichun Li,
Ting Jiang,
Zimiao Luo,
Jianhong Wang,
Zhiqing Pang,
Jun Zhang
Affiliations
Xianping Liu
Department of Radiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China
Yixin Chen
Department of Radiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China
Daoying Geng
Department of Radiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China
Haichun Li
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China
Ting Jiang
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China
Zimiao Luo
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China
Jianhong Wang
National Center for Neurological Disorders, 12 Wulumuqi Middle Road, Shanghai 200040, China
Zhiqing Pang
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 201203, China
Jun Zhang
Department of Radiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China
Biomimetic drug delivery systems, especially red blood cell (RBC) membrane-based nanoparticle drug delivery systems (RNP), have been extensively utilized in tumor drug delivery because of their excellent biocompatibility and prolonged circulation. In this study, we developed an active targeting pH-sensitive RNP loaded with DOX by decorating an aptamer SL1 on RBC membranes (SL1-RNP-DOX) for c-Met-targeted therapy of glioblastoma multiforme (GBM). SL1 could specifically bind to c-Met, which is highly expressed in GBM U87MG cells and facilitate DOX delivery to GBM cells. In vitro studies demonstrated that U87MG cells had a higher uptake of SL1-RNP-DOX (3.25 folds) and a stronger pro-apoptosis effect than unmodified RNP-DOX. In vivo fluorescence imaging and tissue distribution further demonstrated the higher tumor distribution of SL1-RNP-DOX (2.17 folds) compared with RNP-DOX. As a result, SL1-RNP-DOX presented the best anti-GBM effect with a prolonged median survival time (23 days vs. 15.5 days) and the strongest tumor cell apoptosis in vivo among all groups. In conclusion, SL1-RNP-DOX exhibited a promising targeting delivery strategy for GBM therapy.
