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Published on: April 27, 2018
Urinary exosomes-based Engineered Nanovectors for Homologously Targeted Chemo-Chemodynamic Prostate Cancer Therapy
Shaojun Pan1, Yuhui Zhang2, Mark Huang3
1School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China; Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai, 200240, PR China; First Affiliated Hospital of Bengbu Medical College, Bengbu, 233030, China.
Abstract:
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 Exo-PMA/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.
Insights
Researchers developed novel nanovectors using urinary exosomes for targeted prostate cancer therapy. These nanovectors effectively deliver drugs, inhibit tumor growth, and offer a promising, scalable approach for cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Exosomes are promising nanovectors for tumor targeting and immune evasion.
- Current methods for obtaining pure, high-dose exosomes are labor-intensive and challenging.
- Targeted homologous cancer therapy requires efficient and pure nanocarriers.
Purpose of the Study:
- To develop a chemo/chemodynamic theranostic nano-platform for targeted homologous prostate cancer therapy.
- To utilize urinary exosomes as a source for high-purity, functional nanovectors.
- To investigate the therapeutic efficacy of the novel nanovector by targeting specific signaling pathways.
Main Methods:
- Developed Exo-PMA/Fe-HSA@DOX nanovectors cloaked with urinary exosome membrane.
- Utilized urinary exosomes from prostate cancer patients, preserving cancer cell membrane antigens (E-cadherin, CD47).
- Evaluated nanovector penetration in DU145 3D MCTS and in vivo synergistic chemo/chemodynamic therapy, assessing EGFR/AKT/NF-kB/IkB signaling pathway blockage.
Main Results:
- Exo-PMA/Fe-HSA@DOX nanovectors demonstrated high purity and preserved homologous cancer cell targeting properties.
- Nanovectors effectively penetrated prostate cancer models and achieved superior synergistic low-dose chemo/chemodynamic therapy in vivo.
- Therapy successfully abrogated Epidermal Growth Factor Receptor (EGFR) and downstream AKT/NF-kB/IkB signaling.
Conclusions:
- Urinary exosomes provide a rich source for mass production of high-purity nanovectors.
- This novel nano-platform offers an efficient and facile method for targeted homologous prostate cancer therapy.
- The developed nanovectors represent a promising strategy for advancing cancer treatment through targeted drug delivery and pathway inhibition.
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