A Multifunctional Biomimetic Nanoplatform for Relieving Hypoxia to Enhance Chemotherapy and Inhibit the PD-1/PD-L1 Axis.

Abstract

Hypoxia is reported to participate in tumor progression, promote drug resistance, and immune escape within tumor microenvironment, and thus impair therapeutic effects including the chemotherapy and advanced immunotherapy. Here, a multifunctional biomimetic core-shell nanoplatform is reported for improving synergetic chemotherapy and immunotherapy. Based on the properties including good biodegradability and functionalities, the pH-sensitive zeolitic imidazolate framework 8 embedded with catalase and doxorubicin constructs the core and serves as an oxygen generator and drug reservoir. Murine melanoma cell membrane coating on the core provides tumor targeting ability and elicits an immune response due to abundance of antigens. It is demonstrated that this biomimetic core-shell nanoplatform with oxygen generation can be partial to accumulate in tumor and downregulate the expression of hypoxia-inducible factor 1α, which can further enhance the therapeutic effects of chemotherapy and reduce the expression of programmed death ligand 1 (PD-L1). Combined with immune checkpoints blockade therapy by programmed death 1 (PD-1) antibody, the dual inhibition of the PD-1/PD-L1 axis elicits significant immune response and presents a robust effect in lengthening tumor recurrent time and inhibiting tumor metastasis. Consequently, the multifunctional nanoplatform provides a potential strategy of synergetic chemotherapy and immunotherapy.

• Authors: Mei-Zhen Zou, Wen-Long Liu, Chu-Xin Li, Di-Wei Zheng, Jin-Yue Zeng, Fan Gao, Jing-Jie Ye, Xian-Zheng Zhang
• Journal: Small (Weinheim an der Bergstrasse, Germany) (Small) Vol. 14 Issue 28 Pg. e1801120 (07 2018) ISSN: 1613-6829 [Electronic] Germany
• PMID: 29882235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents
• B7-H1 Antigen
• Cytokines
• Hypoxia-Inducible Factor 1, alpha Subunit
• Imidazoles
• Programmed Cell Death 1 Receptor
• acidified zeolitic imidazolate framework-8
• Zeolites
• Doxorubicin
• Catalase
• Oxygen

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• B7-H1 Antigen (metabolism)
• Biomimetics (methods)
• CD8-Positive T-Lymphocytes (metabolism)
• Catalase (metabolism)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cytokines (metabolism)
• Doxorubicin (pharmacology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Imidazoles (chemistry)
• Mice, Inbred C57BL
• Nanoparticles (chemistry, ultrastructure)
• Neoplasms (immunology, pathology)
• Oxygen (pharmacology)
• Programmed Cell Death 1 Receptor (metabolism)
• Signal Transduction
• Tumor Hypoxia (drug effects)
• Zeolites (chemistry)