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Title: Localized degradation of neutrophil extracellular traps by photoregulated enzyme delivery for cancer immunotherapy and metastasis suppression
Authors: Chen, Jiayuan
Hou, Shuai
Liang, Qing
He, Wenshan
Li, Ruiqi
Wang, Haihong
Zhu, Ying
Zhang, Biying
Chen, Lingjuan
Dai, Xiaofang
Zhang, Tao
Ren, Jinghua
Duan, Hongwei
Keywords: Science::Medicine
Issue Date: 2022
Source: Chen, J., Hou, S., Liang, Q., He, W., Li, R., Wang, H., Zhu, Y., Zhang, B., Chen, L., Dai, X., Zhang, T., Ren, J. & Duan, H. (2022). Localized degradation of neutrophil extracellular traps by photoregulated enzyme delivery for cancer immunotherapy and metastasis suppression. ACS Nano, 16(2), 2585-2597.
Project: MOE2018-T2-2-128
Journal: ACS Nano
Abstract: Extrusion of neutrophil extracellular traps (NETs), a fundamental host innate immune defense against pathogens, has recently been linked to cancer resistance to immunotherapy and distant metastasis. These findings highlight interesting areas of cancer-elicited inflammation and potential therapeutic strategies. Disrupting existing NETs with DNase I has been proved to enhance the therapeutic efficacy of tumor immunotherapy and attenuate metastatic spread. However, systemic biodistribution of DNase I raises safety issues, potentially impairing host defense against infection. Hence, tumor-specific delivery and metastatic niche-targeted effects are attractive options for localized degradation of NETs. We have engineered a nanoplatform with a plasmonic gold blackbody (AuPB) core with broad-spectrum photo activity and a mesoporous polydopamine (mPDA) shell for efficient loading and photoregulated release of DNase I. The on-demand released DNase I triggered by the second near-infrared (NIR-II) light irradiation breaks the "NET-mediated physical barrier", thereby increasing the contact of immune cytotoxic cells with tumor cells in living mice and sensitizing immune checkpoint therapy of primary colorectal cancer (CRC). Moreover, the deposition and light-controlled cargo release from systemically delivered AuPB@mPDA carriers in liver, the most frequent site of CRC metastasis, abolished NET-mediated capture of circulating tumor cells and hence metastatic seeding. Our findings indicate that the localized, light-regulated release of DNase I by photoactive carriers in the NIR-II window represent a translational route for immune-mediated tumor regression and metastasis inhibition.
ISSN: 1936-0851
DOI: 10.1021/acsnano.1c09318
Schools: School of Chemical and Biomedical Engineering 
Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Nano, copyright © 2022 American Chemical Society, after peer review and technical editing by the publisher. To access the final edited and published work see
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles
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