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

Kuirong Mao; Xiuxiu Cong; Liangzhu Feng; Hongmei Chen; Jialiang Wang; Chenxi Wu; Kun Liu; Chunsheng Xiao; Yong-Guang Yang; Tianmeng Sun

doi:10.1039/C9BM00226J

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

Kuirong Mao,^abc Xiuxiu Cong,^abc Liangzhu Feng,^e Hongmei Chen,^a Jialiang Wang,^abc Chenxi Wu,^a Kun Liu,

^d Chunsheng Xiao,

^f Yong-Guang Yang*^abcg and Tianmeng Sun

*^abcd

Author affiliations

* Corresponding authors

^a Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Immunology, The First Hospital, Jilin University, Changchun, Jilin, China
E-mail: tsun41@jlu.edu.cn, yongg@jlu.edu.cn

^b International Center of Future Science, Jilin University, Changchun, Jilin, China

^c National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, Jilin, China

^d State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, Jilin, China

^e Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu, China

^f Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry Chinese Academy of Sciences, Changchun, Jilin, China

^g Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA

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.

Biomaterials Science

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

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

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