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Research Article

Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety

Ying Zhou1,2,§, Long Wang1,2,§, Lufei Chen1,§, Wei Wu1,§, Zhimin Yang1,2, Yuanzhuo Wang2,3, Anqi Wang1,2, Sujun Jiang1,2, Xuzhen Qin4( ), Zucheng Ye1( ), Zhiyuan Hu1,2,3,5( ), Zihua Wang1,2( )
Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
School of Nanoscience and Technology, Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China
Department of Laboratory Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing 100730, China
School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China

§ Ying Zhou, Long Wang, Lufei Chen, and Wei Wu contributed equally to this work.

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Graphical Abstract

An effective strategy to engineer glioblastoma (GBM) cell-derived exosomes as biosafe nanocarriers for GBM targeted chemotherapy was developed, offering new possibilities for the application of tumor cell-derived exosomes for brain tumor treatment.

Abstract

Glioblastoma (GBM) has been regarded as one of the most deadly and challenging cancers to treat with extremely poor prognosis. The limited efficacy of current chemotherapies might be attributed to the presence of glioma stem cells (GSCs) as well as the difficulties in passing through the blood–brain barrier (BBB) and targeting tumor cells. Tumor-derived exosomes are emerging as novel and promising drug delivery systems. However, great concerns regarding the biosafety and BBB penetrability remain to be addressed. Herein, we have developed a simple and feasible strategy to engineer GBM cell-derived exosomes with improved biosafety termed “Exo@TDPs” to deliver the cargos of chemotherapeutic agents temozolomide (TMZ) and doxorubicin (DOX) into GBM tissues. Exo@TDPs decorated with angiopep-2 (Ang-2) and CD133-targeted peptides improve the capacity to penetrate the BBB and target tumor cells. Both in vitro and in vivo studies demonstrate that Exo@TDPs can cross the BBB, target GBM cells, penetrate into deep tumor parenchyma, and release the therapeutic cargos effectively. Synergistic delivery of TMZ and DOX by Exo@TDPs exerts therapeutic effects to suppress the tumor growth and prolong the survival time of orthotopic syngeneic mouse GBM models. These findings suggest that our developed Exo@TDPs loaded with chemotherapeutic drugs may bring new possibilities for the application of tumor cell-derived exosomes for brain tumor treatment.

Keywords

glioblastomatumor-derived exosomepeptidetemozolomidedoxorubicintargeted chemotherapy

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Nano Research
Volume 16 Issue 12,
December 2023
Pages 13283-13293
DOI: 10.1007/s12274-023-5921-6
Cite this article:
Zhou Y, Wang L, Chen L, et al. Glioblastoma cell-derived exosomes functionalized with peptides as efficient nanocarriers for synergistic chemotherapy of glioblastoma with improved biosafety. Nano Research, 2023, 16(12): 13283-13293. https://doi.org/10.1007/s12274-023-5921-6
Topics:
Targeted drug delivery
Part of a topical collection:
Special issue for the 20th Anniversary of NCNST

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Received: 31 March 2023
Revised: 10 June 2023
Accepted: 12 June 2023
Published: 05 July 2023
© Tsinghua University Press 2023
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