Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy

Extracellular matrix (ECM) is not only a natural bulwark to shield solid tumor cells from therapeutic agents and cytotoxic T lymphocytes (CTLs), but also one of the key factors that cause tumor hypoxic environment, severely hindering photodynamic reactions and immune responses. In this work, multifu...

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Main Authors: Chen, Xiaokai, Zhang, Xiaodong, Wu, Yinglong, Chen, Yun, Guo, Yi, Jana, Deblin, Wang, Dongdong, Yuan, Wei, Zhao, Yanli
Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/165553
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1655532023-06-21T08:33:09Z Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy Chen, Xiaokai Zhang, Xiaodong Wu, Yinglong Chen, Yun Guo, Yi Jana, Deblin Wang, Dongdong Yuan, Wei Zhao, Yanli School of Chemistry, Chemical Engineering and Biotechnology Science::Chemistry Nanomedicine Calcium Ion Therapy Extracellular matrix (ECM) is not only a natural bulwark to shield solid tumor cells from therapeutic agents and cytotoxic T lymphocytes (CTLs), but also one of the key factors that cause tumor hypoxic environment, severely hindering photodynamic reactions and immune responses. In this work, multifunctional nanoscavengers (ECMT NS) consisting of digestive enzyme chymotrypsin, catalase, calcium peroxide nanoparticles, photosensitizer chlorin e6, and tumor ECM-targeting CLT1 peptide are rationally designed with several benefits for enhanced cocktail calcium ion/photodynamic/immune therapy. The scavengers can effectively “clear” tumor ECM via digestive proteolytic enzyme- and reactive oxygen species-mediated pathways, deepening tumor penetration of the scavengers and CTLs. Thanks to the ECM destruction and oxygen self-supply capability of ECMT NS, the hypoxia in tumors is attenuated, thus improving photodynamic therapeutic efficiency and downregulating immunosuppressive factors. Moreover, the combination of calcium ion overload and photodynamic therapy enriches damage-associated molecular patterns, which promotes CTL activation to inhibit abscopal tumor growth and lung metastasis. The presented ECM destruction strategy provides a solution to overcome the tumor suppressive microenvironment. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Submitted/Accepted version This work was supported by the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081) and the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03). 2023-03-31T01:57:53Z 2023-03-31T01:57:53Z 2022 Journal Article Chen, X., Zhang, X., Wu, Y., Chen, Y., Guo, Y., Jana, D., Wang, D., Yuan, W. & Zhao, Y. (2022). Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy. Materials Today, 61, 78-90. https://dx.doi.org/10.1016/j.mattod.2022.10.018 1369-7021 https://hdl.handle.net/10356/165553 10.1016/j.mattod.2022.10.018 61 78 90 en A20E5c0081 NRF-NRFI2018-03 Materials Today © 2022 Elsevier Ltd. All rights reserved. This paper was published in Materials Today and is made available with permission of Elsevier Ltd. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Chemistry
Nanomedicine
Calcium Ion Therapy
spellingShingle Science::Chemistry
Nanomedicine
Calcium Ion Therapy
Chen, Xiaokai
Zhang, Xiaodong
Wu, Yinglong
Chen, Yun
Guo, Yi
Jana, Deblin
Wang, Dongdong
Yuan, Wei
Zhao, Yanli
Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy
description Extracellular matrix (ECM) is not only a natural bulwark to shield solid tumor cells from therapeutic agents and cytotoxic T lymphocytes (CTLs), but also one of the key factors that cause tumor hypoxic environment, severely hindering photodynamic reactions and immune responses. In this work, multifunctional nanoscavengers (ECMT NS) consisting of digestive enzyme chymotrypsin, catalase, calcium peroxide nanoparticles, photosensitizer chlorin e6, and tumor ECM-targeting CLT1 peptide are rationally designed with several benefits for enhanced cocktail calcium ion/photodynamic/immune therapy. The scavengers can effectively “clear” tumor ECM via digestive proteolytic enzyme- and reactive oxygen species-mediated pathways, deepening tumor penetration of the scavengers and CTLs. Thanks to the ECM destruction and oxygen self-supply capability of ECMT NS, the hypoxia in tumors is attenuated, thus improving photodynamic therapeutic efficiency and downregulating immunosuppressive factors. Moreover, the combination of calcium ion overload and photodynamic therapy enriches damage-associated molecular patterns, which promotes CTL activation to inhibit abscopal tumor growth and lung metastasis. The presented ECM destruction strategy provides a solution to overcome the tumor suppressive microenvironment.
author2 School of Chemistry, Chemical Engineering and Biotechnology
author_facet School of Chemistry, Chemical Engineering and Biotechnology
Chen, Xiaokai
Zhang, Xiaodong
Wu, Yinglong
Chen, Yun
Guo, Yi
Jana, Deblin
Wang, Dongdong
Yuan, Wei
Zhao, Yanli
format Article
author Chen, Xiaokai
Zhang, Xiaodong
Wu, Yinglong
Chen, Yun
Guo, Yi
Jana, Deblin
Wang, Dongdong
Yuan, Wei
Zhao, Yanli
author_sort Chen, Xiaokai
title Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy
title_short Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy
title_full Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy
title_fullStr Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy
title_full_unstemmed Tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy
title_sort tumor extracellular matrix-targeted nanoscavengers reverse suppressive microenvironment for cocktail therapy
publishDate 2023
url https://hdl.handle.net/10356/165553
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