Engineered macrophages as near-infrared light activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer

Yanjuan Huang, Zilin Guan, Xiuling Dai, Yifeng Shen, Qin Wei, Lingling Ren, Jingwen Jiang, Zhanghong Xiao, Yali Jiang, Di Liu, Zeqian Huang, Xiaoyu Xu, Yong Luo and Chunshun Zhao ()
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Yanjuan Huang: Sun Yat-sen University
Zilin Guan: Sun Yat-sen University
Xiuling Dai: Sun Yat-sen University
Yifeng Shen: Sun Yat-sen University
Qin Wei: Sun Yat-sen University
Lingling Ren: Sun Yat-sen University
Jingwen Jiang: Sun Yat-sen University
Zhanghong Xiao: Sun Yat-sen University
Yali Jiang: Sun Yat-sen University
Di Liu: Sun Yat-sen University
Zeqian Huang: Sun Yat-sen University
Xiaoyu Xu: Sun Yat-sen University
Yong Luo: Sun Yat-sen University
Chunshun Zhao: Sun Yat-sen University

Nature Communications, 2021, vol. 12, issue 1, 1-22

Abstract: Abstract Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In this work, engineered macrophages (Oxa(IV)@ZnPc@M) carrying nanomedicine containing oxaliplatin prodrug and photosensitizer are designed as near-infrared (NIR) light-activated drug vectors, aiming to achieve enhanced chemo/photo/immunotherapy of primary and bone metastatic tumors. Oxa(IV)@ZnPc@M exhibits an anti-tumor M1 phenotype polarization and can efficiently home to primary and bone metastatic tumors. Additionally, therapeutics inside Oxa(IV)@ZnPc@M undergo NIR triggered release, which can kill primary tumors via combined chemo-photodynamic therapy and induce immunogenic cell death simultaneously. Oxa(IV)@ZnPc@M combined with anti-PD-L1 can eliminate primary and bone metastatic tumors, activate tumor-specific antitumor immune response, and improve overall survival with limited systemic toxicity. Therefore, this all-in-one macrophage provides a treatment platform for effective therapy of primary and bone metastatic tumors.

Date: 2021
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DOI: 10.1038/s41467-021-24564-0

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