Single-Component Dual-Functional Autoboost Strategy by Dual Photodynamic and Cyclooxygenase-2 Inhibition for Lung Cancer and Spinal Metastasis
© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH..
Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single-component dual-functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)-generated HOCl. A representative prodrug (DHU-CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU-CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU-CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase-2 (COX-2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX-2. Downstream prostaglandins E2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU-CBA2 promotes infiltration and function of CD8+ T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single-component dual-functional prodrug activated by TME-specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX-2 inhibitor.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 11(2024), 12 vom: 15. März, Seite e2303981 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Ben [VerfasserIn] |
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| Links: |
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| Themen: |
COX‐2 |
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| Anmerkungen: |
Date Completed 28.03.2024 Date Revised 29.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/advs.202303981 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single-component dual-functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)-generated HOCl. A representative prodrug (DHU-CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU-CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU-CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase-2 (COX-2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX-2. Downstream prostaglandins E2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU-CBA2 promotes infiltration and function of CD8+ T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single-component dual-functional prodrug activated by TME-specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX-2 inhibitor | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a COX‐2 | |
| 650 | 4 | |a HOCl response | |
| 650 | 4 | |a immune activation | |
| 650 | 4 | |a photodynamic therapy | |
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| 700 | 1 | |a Lu, Zhen-Ni |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Meng-Xiong |e verfasserin |4 aut | |
| 700 | 1 | |a He, Xiao-Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Zhi-Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Hai-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Hong-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Li-Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Jian |e verfasserin |4 aut | |
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