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Theranostics 2020; 10(26):11998-12010. doi:10.7150/thno.50806 This issue Cite

Research Paper

In situ tuning proangiogenic factor-mediated immunotolerance synergizes the tumoricidal immunity via a hypoxia-triggerable liposomal bio-nanoreactor

Chen Chen1, Shengchang Zhang1, Rui Zhang1, Peng Sun2, Chongdeng Shi1, Mohnad Abdalla1, Anning Li3, Jiawen Xu4,5, Wei Du1, Jing Zhang1, Ying Liu1, Chunwei Tang1, Zhenmei Yang1, Xinyi Jiang1✉

1. Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Shandong Province 250012, PR China.
2. Shandong University of Traditional Chinese Medicine, 4655 University Road, Shandong Province 250355, PR China.
3. Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Cultural West Road, Shandong Province 250012, PR China.
4. Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Five Weft Seven Road, Shandong Province 250021, PR China.
5. Department of Pathology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 324 Five Weft Seven Road, Shandong Province 250021, PR China.

✉ Corresponding author: Xinyi Jiang, Ph.D., Professor, Phone/Fax: +86-0531-88382015; E-mail: xinyijiangedu.cn.

Citation:
Chen C, Zhang S, Zhang R, Sun P, Shi C, Abdalla M, Li A, Xu J, Du W, Zhang J, Liu Y, Tang C, Yang Z, Jiang X. In situ tuning proangiogenic factor-mediated immunotolerance synergizes the tumoricidal immunity via a hypoxia-triggerable liposomal bio-nanoreactor. Theranostics 2020; 10(26):11998-12010. doi:10.7150/thno.50806. https://www.thno.org/v10p11998.htm
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Abstract

Graphic abstract

Rationale: Vascular abnormality stemming from the hypoxia-driven elevation of proangiogenic factors is a hallmark for many solid malignant tumors, including colorectal cancer (CRC) and its liver metastasis. We report a hypoxia-triggered liposome-supported metal-polyphenol-gene bio-nanoreactor to tune the proangiogenic factor-mediated immunotolerance and synergize the elicited tumoricidal immunity for CRC treatment.

Methods: With the aid of polyphenol gallic acid, Cu2+ ion-based intracellular bio-nanoreactor was synthesized for the delivery of small interfering RNA targeting vascular endothelial growth factor and then cloaked with a hybrid liposomal membrane that harbored a hypoxia-responsive azobenzene derivative. In hypoxic tumor, the liposomal shell disintegrated, and a shrunk-size bio-nanoreactor was burst released. Intracellularly, Cu2+ from the bio-nanoreactor catalyzed a Fenton-like reaction with glutathione, which efficiently converted H2O2 to •OH and enabled a chemodynamic therapy (CDT) in tumor sites. With the alleviation of proangiogenic factor-mediated immunotolerance and high production of CDT-induced tumor-associated antigens, robust tumoricidal immunity was co-stimulated.

Results: With colorectal tumor and its liver metastasis models, we determined the underlying mechanism of proangiogenic factor-mediated immunotolerance and highlighted that the liposomal bio-nanoreactor could create positive feedback among the critical players in the vascular endothelium and synergize the elicited tumoricidal immunity.

Conclusion: Our work provides an alternative strategy for exerting efficient tumoricidal immunity in the proangiogenic factor-upregulated subpopulation of CRC patients and may have a wide-ranging impact on cancer immune-anti-angiogenic complementary therapy in clinics.

Keywords: Hypoxia-triggered liposome, Metal-polyphenol-gene bio-nanoreactor, Proangiogenic factor, Immunotolerance, Chemodynamic therapy

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APA
Chen, C., Zhang, S., Zhang, R., Sun, P., Shi, C., Abdalla, M., Li, A., Xu, J., Du, W., Zhang, J., Liu, Y., Tang, C., Yang, Z., Jiang, X. (2020). In situ tuning proangiogenic factor-mediated immunotolerance synergizes the tumoricidal immunity via a hypoxia-triggerable liposomal bio-nanoreactor. Theranostics, 10(26), 11998-12010. https://doi.org/10.7150/thno.50806.

ACS
Chen, C.; Zhang, S.; Zhang, R.; Sun, P.; Shi, C.; Abdalla, M.; Li, A.; Xu, J.; Du, W.; Zhang, J.; Liu, Y.; Tang, C.; Yang, Z.; Jiang, X. In situ tuning proangiogenic factor-mediated immunotolerance synergizes the tumoricidal immunity via a hypoxia-triggerable liposomal bio-nanoreactor. Theranostics 2020, 10 (26), 11998-12010. DOI: 10.7150/thno.50806.

NLM
Chen C, Zhang S, Zhang R, Sun P, Shi C, Abdalla M, Li A, Xu J, Du W, Zhang J, Liu Y, Tang C, Yang Z, Jiang X. In situ tuning proangiogenic factor-mediated immunotolerance synergizes the tumoricidal immunity via a hypoxia-triggerable liposomal bio-nanoreactor. Theranostics 2020; 10(26):11998-12010. doi:10.7150/thno.50806. https://www.thno.org/v10p11998.htm

CSE
Chen C, Zhang S, Zhang R, Sun P, Shi C, Abdalla M, Li A, Xu J, Du W, Zhang J, Liu Y, Tang C, Yang Z, Jiang X. 2020. In situ tuning proangiogenic factor-mediated immunotolerance synergizes the tumoricidal immunity via a hypoxia-triggerable liposomal bio-nanoreactor. Theranostics. 10(26):11998-12010.

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