期刊
BIOMATERIALS
卷 275, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.120946
关键词
Urinary exosome; Nanovectors; Fenton reaction; Targeted prostate cancer therapy
资金
- National Key Research and Development Projects [2017YFA0205301, 2016YFA0201200]
- International Cooperation and Exchanges Projects of National Natural Science Foundation of China [82020108017]
- National Natural Science Foundation of China [81903169]
- Innovative Team project of National Natural Science Foundation of China [81921002]
- Shanghai Sailing Program [19YF1422300]
- Shanghai Jiao Tong University Transformation Medicine Cross Research Fund [ZH2018QNB25, ZH2018QNB26]
- Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument [15DZ2252000]
- China Postdoctoral Science Foundation [2020TQ0191]
The utilization of urinary exosomes as nanovectors for homologous prostate cancer therapy shows promising results in targeted treatment and signal pathway inhibition, offering a potential solution for mass production of such nanovectors in the future.
Multi-functional nanovectors based on exosomes from cancer cell culture supernatants in vitro has been successfully utilized for tumor-specific targeting and immune escape. However, the labor-intensive purification procedures for rich-dose and high-purity homogeneous exosomes without using targeting ligands are still a challenging task. Herein, we developed a nanovector Exo-PMA/Fe-HSA@DOX through cloaked by urinary exosome membrane as a chemo/chemodynamic theranostic nano-platform for targeted homologous prostate cancer therapy which pertain to the abrogation of Epidermal Growth Factor Receptor (EGFR) and its downstream AKT/NF-kB/IkB signaling instead of ERK signaling cascades. Urinary exosomes-based nanovectors own the same urological cancer cell membrane antigen inclusive of E-cadherin, CD 47 and are free from intracellular substance such as Histone 3 and COX IV. The targeting properties of the homologous cancer cell are well preserved in ExoPMA/Fe-HSA@DOX nanovectors in high purity. Meanwhile, the nanovectors based on urinary exosomes from prostate patients deeply penetrated into prostate cancer DU145 3D MCTS, and successfully achieve superior synergistic low-dose chemo/chemodynamic performance in vivo. In addition, the blockage of bypassing EGFR/ AKT/NF-kB/IkB signaling pathway is greatly enhanced via elevated intracellular PMA/Fe-HSA@DOX nanoparticles (NPs). It is expected that the rich source and high purity of urinary exosomes offer a reliable solution for mass production of such nanovectors in the future. The targeted homologous cancer therapy based on the urinary exosomes from cancer patients exemplifies a novel targeted anticancer scheme with efficient and facile method.
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