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Enzyme-instructed assembly of a cholesterol conjugate promotes pro-inflammatory macrophages and induces apoptosis of cancer cells

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Abstract

The combination of immunotherapy and chemotherapy has shown great potential for treating solid tumors. Although various combination therapy regimens have been demonstrated to be effective, their implementation in practice always needs separate drugs or modalities, which in turn requires specific and complicated operation procedures. Here, we describe the use of enzyme-instructed self-assembly (EISA) of a phosphotyrosine–cholesterol (PTC) conjugate to combine immune microenvironment modulation and chemotherapy. The enzymatic dephosphorylation of PTC results in the assembly of its derivatives inside and outside the cells, which leads to repolarization of the macrophage phenotype and direct death of cancer cells. The generation of reactive oxygen species and actin disturbance induced by the assemblies has been verified relative to the macrophage repolarization. We also demonstrate its dual repolarization and inhibition effects in vivo using an ovarian cancer bearing immunocompetent murine model. The EISA of cholesterol conjugates is an effective yet simple approach for the combination of tumor microenvironment immunomodulation and chemotherapy.

Graphical abstract: Enzyme-instructed assembly of a cholesterol conjugate promotes pro-inflammatory macrophages and induces apoptosis of cancer cells

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Article information


Submitted
21 Jan 2020
Accepted
11 Feb 2020
First published
12 Feb 2020

Biomater. Sci., 2020, Advance Article
Article type
Paper

Enzyme-instructed assembly of a cholesterol conjugate promotes pro-inflammatory macrophages and induces apoptosis of cancer cells

Y. Hu, H. Wang, C. Li, J. Liu, B. Xu and W. Di, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/D0BM00125B

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