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A Multifunctional Biomimetic Nanoplatform for Relieving Hypoxia to Enhance Chemotherapy and Inhibit the PD‐1/PD‐L1 Axis
Author(s) -
Zou MeiZhen,
Liu WenLong,
Li ChuXin,
Zheng DiWei,
Zeng JinYue,
Gao Fan,
Ye JingJie,
Zhang XianZheng
Publication year - 2018
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201801120
Subject(s) - immunotherapy , tumor microenvironment , immune system , cancer research , chemotherapy , hypoxia (environmental) , tumor hypoxia , immunogenic cell death , doxorubicin , drug delivery , medicine , materials science , chemistry , immunology , nanotechnology , radiation therapy , oxygen , organic chemistry
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.