Activatable immunoprotease nanorestimulator for second near-infrared photothermal immunotherapy of cancer
Photothermal immunotherapy is a combinational cancer therapy modality, wherein the photothermal process can noninvasively ablate cancer and efficiently trigger cancer immunogenic cell death to ignite antitumor immunity. However, cancer cells can resist the cytotoxic lymphocyte-mediated antitumor eff...
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sg-ntu-dr.10356-1702892023-09-06T02:01:16Z Activatable immunoprotease nanorestimulator for second near-infrared photothermal immunotherapy of cancer Xu, Mengke Zhang, Chi He, Shasha Xu, Cheng Wei, Xin Pu, Kanyi School of Chemistry, Chemical Engineering and Biotechnology Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Cancer Therapy Immunoprotease Restimulation Photothermal immunotherapy is a combinational cancer therapy modality, wherein the photothermal process can noninvasively ablate cancer and efficiently trigger cancer immunogenic cell death to ignite antitumor immunity. However, cancer cells can resist the cytotoxic lymphocyte-mediated antitumor effect via expressing serine protease inhibitory proteins (serpins) to deactivate proteolytic immunoproteases. Herein, we report a smart polymer nanoagonist (SPND) with second near-infrared (NIR-II) phototherapeutic ablation and tumor-specific immunoprotease granzyme B (GrB) restimulation for cancer photothermal immunotherapy. SPND has a semiconducting polymer backbone grafted with a small-molecule inhibitor of serpinB9 (Sb9i) via a glutathione (GSH)-cleavable linker. Once in the tumor, Sb9i can be specifically liberated from SPND to inhibit serpinB9, restimulating the activity of GrB to enhance cancer immunotherapy. Moreover, SPND induces photothermal therapy for direct tumor ablation and immunogenic cancer cell death (ICD) under NIR-II photoirradiation. Therefore, such a smart nanoagonist represents a way toward combination photothermal immunotherapy (PTI). Ministry of Education (MOE) National Research Foundation (NRF) K.P. thanks Singapore National Research Foundation (NRF) (NRF-NRFI07-2021-0005) as well as Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20) Academic Research Fund Tier 2 (MOE-T2EP30220-0010; MOE-T2EP30221-0004) for the financial support. 2023-09-06T02:01:16Z 2023-09-06T02:01:16Z 2023 Journal Article Xu, M., Zhang, C., He, S., Xu, C., Wei, X. & Pu, K. (2023). Activatable immunoprotease nanorestimulator for second near-infrared photothermal immunotherapy of cancer. ACS Nano, 17(9), 8183-8194. https://dx.doi.org/10.1021/acsnano.2c12066 1936-0851 https://hdl.handle.net/10356/170289 10.1021/acsnano.2c12066 37122103 2-s2.0-85156198308 9 17 8183 8194 en NRF-NRFI07-2021-0005 2019-T1-002-045 RG125/19 RT05/20 MOE-T2EP30220-0010 MOE-T2EP30221-0004 ACS Nano © 2023 American Chemical Society. All rights reserved. |
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Science::Medicine Cancer Therapy Immunoprotease Restimulation Xu, Mengke Zhang, Chi He, Shasha Xu, Cheng Wei, Xin Pu, Kanyi Activatable immunoprotease nanorestimulator for second near-infrared photothermal immunotherapy of cancer |
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Photothermal immunotherapy is a combinational cancer therapy modality, wherein the photothermal process can noninvasively ablate cancer and efficiently trigger cancer immunogenic cell death to ignite antitumor immunity. However, cancer cells can resist the cytotoxic lymphocyte-mediated antitumor effect via expressing serine protease inhibitory proteins (serpins) to deactivate proteolytic immunoproteases. Herein, we report a smart polymer nanoagonist (SPND) with second near-infrared (NIR-II) phototherapeutic ablation and tumor-specific immunoprotease granzyme B (GrB) restimulation for cancer photothermal immunotherapy. SPND has a semiconducting polymer backbone grafted with a small-molecule inhibitor of serpinB9 (Sb9i) via a glutathione (GSH)-cleavable linker. Once in the tumor, Sb9i can be specifically liberated from SPND to inhibit serpinB9, restimulating the activity of GrB to enhance cancer immunotherapy. Moreover, SPND induces photothermal therapy for direct tumor ablation and immunogenic cancer cell death (ICD) under NIR-II photoirradiation. Therefore, such a smart nanoagonist represents a way toward combination photothermal immunotherapy (PTI). |
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School of Chemistry, Chemical Engineering and Biotechnology |
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School of Chemistry, Chemical Engineering and Biotechnology Xu, Mengke Zhang, Chi He, Shasha Xu, Cheng Wei, Xin Pu, Kanyi |
format |
Article |
author |
Xu, Mengke Zhang, Chi He, Shasha Xu, Cheng Wei, Xin Pu, Kanyi |
author_sort |
Xu, Mengke |
title |
Activatable immunoprotease nanorestimulator for second near-infrared photothermal immunotherapy of cancer |
title_short |
Activatable immunoprotease nanorestimulator for second near-infrared photothermal immunotherapy of cancer |
title_full |
Activatable immunoprotease nanorestimulator for second near-infrared photothermal immunotherapy of cancer |
title_fullStr |
Activatable immunoprotease nanorestimulator for second near-infrared photothermal immunotherapy of cancer |
title_full_unstemmed |
Activatable immunoprotease nanorestimulator for second near-infrared photothermal immunotherapy of cancer |
title_sort |
activatable immunoprotease nanorestimulator for second near-infrared photothermal immunotherapy of cancer |
publishDate |
2023 |
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https://hdl.handle.net/10356/170289 |
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1779156441726189568 |