Nanodrugs mediate TAMs-related arginine metabolism interference to boost photodynamic immunotherapy
Copyright © 2024 Elsevier B.V. All rights reserved..
As a potential treatment strategy for low immunogenic triple negative breast cancer (TNBC), photodynamic therapy (PDT) induced antitumor immunotherapy is greatly limited by the immunosuppressive tumor microenvironment (ITM), especially the M2 phenotype tumor-associated macrophages (TAMs). The balance of arginine metabolism plays an important role in TAMs polarization. Herein, a multifunctional nanoplatform (defined as HN-HFPA) was employed to burst the anti-tumor immunity of TNBC post PDT by reeducating TAMs through interfering the TAMs-associated arginine metabolism. The L-arginine (L-Arg) was loaded in the hollow cavity of HN-HFPA, which could not only generate nitric oxide (NO) for tumor therapy, but also serve as a substrate of arginine metabolism pathway. As an inhibitor of arginases-1 (Arg-1) of M2 TAMs, L-norvaline (L-Nor) was modified to the hyaluronic acid (HA), and coated in the surface of HFPA. After degradation of HA by hyaluronidase in tumor tissue and GSH-mediated disintegration, HN-HFPA depleted intracellular GSH, produced remarkable reactive oxygen species (ROS) under light irradiation and released L-Arg to generate NO, which induced tumor immunogenic cell death (ICD). Real-time ultrasound imaging of tumor was realized taking advantage of the gas feature of NO. The L-Nor suppressed the Arg-1 overexpressed in M2, which skewed the balance of arginine metabolism and reversed the ITM with increased ratios of M1 and CD8+ T cells, finally resulted in amplified antitumor immune response and apparent tumor metastasis inhibition. This study remodeled ITM to strengthen immune response post PDT, which provided a promising treatment strategy for TNBC.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:367 |
|---|---|
| Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 367(2024) vom: 31. März, Seite 248-264 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chen, Yi [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jconrel.2024.01.045 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367628171 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367628171 | ||
| 003 | DE-627 | ||
| 005 | 20240326235308.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240126s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jconrel.2024.01.045 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1348.xml |
| 035 | |a (DE-627)NLM367628171 | ||
| 035 | |a (NLM)38272398 | ||
| 035 | |a (PII)S0168-3659(24)00060-9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chen, Yi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Nanodrugs mediate TAMs-related arginine metabolism interference to boost photodynamic immunotherapy |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.03.2024 | ||
| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a As a potential treatment strategy for low immunogenic triple negative breast cancer (TNBC), photodynamic therapy (PDT) induced antitumor immunotherapy is greatly limited by the immunosuppressive tumor microenvironment (ITM), especially the M2 phenotype tumor-associated macrophages (TAMs). The balance of arginine metabolism plays an important role in TAMs polarization. Herein, a multifunctional nanoplatform (defined as HN-HFPA) was employed to burst the anti-tumor immunity of TNBC post PDT by reeducating TAMs through interfering the TAMs-associated arginine metabolism. The L-arginine (L-Arg) was loaded in the hollow cavity of HN-HFPA, which could not only generate nitric oxide (NO) for tumor therapy, but also serve as a substrate of arginine metabolism pathway. As an inhibitor of arginases-1 (Arg-1) of M2 TAMs, L-norvaline (L-Nor) was modified to the hyaluronic acid (HA), and coated in the surface of HFPA. After degradation of HA by hyaluronidase in tumor tissue and GSH-mediated disintegration, HN-HFPA depleted intracellular GSH, produced remarkable reactive oxygen species (ROS) under light irradiation and released L-Arg to generate NO, which induced tumor immunogenic cell death (ICD). Real-time ultrasound imaging of tumor was realized taking advantage of the gas feature of NO. The L-Nor suppressed the Arg-1 overexpressed in M2, which skewed the balance of arginine metabolism and reversed the ITM with increased ratios of M1 and CD8+ T cells, finally resulted in amplified antitumor immune response and apparent tumor metastasis inhibition. This study remodeled ITM to strengthen immune response post PDT, which provided a promising treatment strategy for TNBC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Arginine metabolism | |
| 650 | 4 | |a Immunogenic cell death | |
| 650 | 4 | |a Photodynamic therapy | |
| 650 | 4 | |a Tumor-associated macrophages reprogramming | |
| 650 | 7 | |a Arginine |2 NLM | |
| 650 | 7 | |a 94ZLA3W45F |2 NLM | |
| 650 | 7 | |a Hyaluronic Acid |2 NLM | |
| 650 | 7 | |a 9004-61-9 |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Nitric Oxide |2 NLM | |
| 650 | 7 | |a 31C4KY9ESH |2 NLM | |
| 700 | 1 | |a Shu, Xian |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Jia-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Shi-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Jin-Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jia-Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Li-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Ping |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of controlled release : official journal of the Controlled Release Society |d 1996 |g 367(2024) vom: 31. März, Seite 248-264 |w (DE-627)NLM085820296 |x 1873-4995 |7 nnns |
| 773 | 1 | 8 | |g volume:367 |g year:2024 |g day:31 |g month:03 |g pages:248-264 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jconrel.2024.01.045 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 367 |j 2024 |b 31 |c 03 |h 248-264 | ||