Double-drug loading upconversion nanoparticles for monitoring and therapy of a MYC/BCL6-positive double-hit diffuse large B-cell lymphoma
Copyright © 2022 Elsevier Ltd. All rights reserved..
Diffuse large B-cell lymphoma (DLBCL) is a systemic hematological malignancy. Herein, through whole exome sequencing (WES), we found that DLBCL genome changes and expression characteristics are associated with various immune cells. Lenalidomide (Len) is a leading candidate for the immunomodulatory treatment of multiple myeloma in the clinic. Inspired by lenalidomide as an immunomodulatory drug for the treatment of multiple myeloma, we constructed a multifunctional nanoplatform with therapeutic and imaging properties for DLBCL by co-loading lenalidomide and dexamethasone (Dex) with upconversion nanoparticles using a GSH-sensitive linker (named as UCNPs-Len-Dex). In vitro cell experiments proved that the UCNPs-Len-Dex had good biocompatibility and obvious antitumor efficacy. UCNPs-Len-Dex also exhibited excellent anti-tumor efficacy and imaging properties in vivo. RNA sequencing showed that UCNPs-Len-Dex targeted and activated the E3 ligase of CRBN, resulting in IKZF1/3 degradation, which inhibited MYC/BCL6-positive DLBCL and maintained the stability of the immune microenvironment. Therefore, this study provided a new monitoring and therapeutic synergetic strategy for DLBCL.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:287 |
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| Enthalten in: |
Biomaterials - 287(2022) vom: 30. Aug., Seite 121607 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Yulu [VerfasserIn] |
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| Links: |
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| Themen: |
DLBCL |
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| Anmerkungen: |
Date Revised 16.10.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.biomaterials.2022.121607 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2022 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Diffuse large B-cell lymphoma (DLBCL) is a systemic hematological malignancy. Herein, through whole exome sequencing (WES), we found that DLBCL genome changes and expression characteristics are associated with various immune cells. Lenalidomide (Len) is a leading candidate for the immunomodulatory treatment of multiple myeloma in the clinic. Inspired by lenalidomide as an immunomodulatory drug for the treatment of multiple myeloma, we constructed a multifunctional nanoplatform with therapeutic and imaging properties for DLBCL by co-loading lenalidomide and dexamethasone (Dex) with upconversion nanoparticles using a GSH-sensitive linker (named as UCNPs-Len-Dex). In vitro cell experiments proved that the UCNPs-Len-Dex had good biocompatibility and obvious antitumor efficacy. UCNPs-Len-Dex also exhibited excellent anti-tumor efficacy and imaging properties in vivo. RNA sequencing showed that UCNPs-Len-Dex targeted and activated the E3 ligase of CRBN, resulting in IKZF1/3 degradation, which inhibited MYC/BCL6-positive DLBCL and maintained the stability of the immune microenvironment. Therefore, this study provided a new monitoring and therapeutic synergetic strategy for DLBCL | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DLBCL | |
| 650 | 4 | |a Dexamethasone | |
| 650 | 4 | |a Lenalidomide | |
| 650 | 4 | |a Multi-omics analysis | |
| 650 | 4 | |a Upconversion nanoparticles | |
| 700 | 1 | |a Chen, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Weihu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Wuzhe |e verfasserin |4 aut | |
| 700 | 1 | |a Gou, Shuangquan |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Pengfei |e verfasserin |4 aut | |
| 700 | 1 | |a He, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Kaiyong |e verfasserin |4 aut | |
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