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Issue 7, 2019
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Intratumoral delivery of M-CSF by calcium crosslinked polymer micelles enhances cancer immunotherapy

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Abstract

Immunotherapy has shown promising results in multiple malignancies. However, there are still significant challenges in cancer immunotherapy including the powerful immunosuppressive tumor microenvironment and adverse off-target side effects. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges faced by cancer immunotherapy. Here, a tumor acidity-responsive biomacromolecule delivery system was designed to intratumorally deliver an immune-activating cytokine, macrophage colony-stimulating factor (M-CSF) and attenuate the acidic microenvironment. This nanoparticle was prepared by introducing CaCO3 as a crosslinker to form an M-CSF-loaded stable micelle (NP/M-CSF/CaCO3). Administration of NP/M-CSF/CaCO3 significantly inhibited tumor growth by enhancing T cell-mediated anti-tumor immune responses and reversing the TAM-mediated immunosuppression. This study provides new avenues for cascade amplification of the antitumor effects by targeting the tumor microenvironment. This approach may also help avoid unwanted complications.

Graphical abstract: Intratumoral delivery of M-CSF by calcium crosslinked polymer micelles enhances cancer immunotherapy

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Supplementary files

Article information


Submitted
12 Feb 2019
Accepted
11 Apr 2019
First published
12 Apr 2019

Biomater. Sci., 2019,7, 2769-2776
Article type
Paper

Intratumoral delivery of M-CSF by calcium crosslinked polymer micelles enhances cancer immunotherapy

K. Mao, X. Cong, L. Feng, H. Chen, J. Wang, C. Wu, K. Liu, C. Xiao, Y. Yang and T. Sun, Biomater. Sci., 2019, 7, 2769
DOI: 10.1039/C9BM00226J

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