"Three-in-one" : A Photoactivable Nanoplatform Evokes Anti-Immune Response by Inhibiting BRD4-cMYC-PDL1 Axis to Intensify Photo-Immunotherapy
© 2024 Wiley‐VCH GmbH..
Combinatorial immuno-cancer therapy is recognized as a promising approach for efficiently treating malignant tumors. Yet, the development of multifunctional nanomedicine capable of precise tumor targeting, remote activation, and immune-regulating drug delivery remains a significant challenge. In this study, nanoparticles loaded with an immune checkpoint inhibitor (JQ-1) using polypyrrole/hyaluronic acid (PPyHA/JQ-1) are developed. These nanoparticles offer active tumor targeting, photothermal tumor ablation using near-infrared light, and laser-controlled JQ-1 release for efficient breast cancer treatment. When the molecular weight of HA varies (from 6.8 kDa to 3 MDa) in the PPyHA nanoparticles, it is found that the nanoparticles synthesized using 1 MDa HA, referred to as PPyHA (1 m), show the most suitable properties, including small hydrodynamic size, high surface HA contents, and colloidal stability. Upon 808 nm laser irradiation, PPyHA/JQ-1 elevates the temperature above 55 °C, which is sufficient for thermal ablation and active release of JQ-1 in the tumor microenvironment (TME). Notably, the controlled release of JQ-1 substantially inhibits the expression of cancer-promoting genes. Furthermore, PPyHA/JQ-1 effectively suppresses the expression of programmed cell death ligand 1 (PD-L1) and prolongs dendritic cell maturation and CD8+ T cell activation against the tumor both in vitro and in vivo. PPyHA/JQ-1 treatment simultaneously provides a significant tumor regression through photothermal therapy and immune checkpoint blockade, leading to a durable antitumor-immune response. Overall, "Three-in-one" immunotherapeutic photo-activable nanoparticles have the potential to be beneficial for a targeted combinatorial treatment approach for TNBC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Advanced healthcare materials - (2024) vom: 26. Feb., Seite e2304093 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mohanty, Ayeskanta [VerfasserIn] |
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| Links: |
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| Themen: |
Breast cancer |
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| Anmerkungen: |
Date Revised 29.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1002/adhm.202304093 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368998770 |
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| 520 | |a Combinatorial immuno-cancer therapy is recognized as a promising approach for efficiently treating malignant tumors. Yet, the development of multifunctional nanomedicine capable of precise tumor targeting, remote activation, and immune-regulating drug delivery remains a significant challenge. In this study, nanoparticles loaded with an immune checkpoint inhibitor (JQ-1) using polypyrrole/hyaluronic acid (PPyHA/JQ-1) are developed. These nanoparticles offer active tumor targeting, photothermal tumor ablation using near-infrared light, and laser-controlled JQ-1 release for efficient breast cancer treatment. When the molecular weight of HA varies (from 6.8 kDa to 3 MDa) in the PPyHA nanoparticles, it is found that the nanoparticles synthesized using 1 MDa HA, referred to as PPyHA (1 m), show the most suitable properties, including small hydrodynamic size, high surface HA contents, and colloidal stability. Upon 808 nm laser irradiation, PPyHA/JQ-1 elevates the temperature above 55 °C, which is sufficient for thermal ablation and active release of JQ-1 in the tumor microenvironment (TME). Notably, the controlled release of JQ-1 substantially inhibits the expression of cancer-promoting genes. Furthermore, PPyHA/JQ-1 effectively suppresses the expression of programmed cell death ligand 1 (PD-L1) and prolongs dendritic cell maturation and CD8+ T cell activation against the tumor both in vitro and in vivo. PPyHA/JQ-1 treatment simultaneously provides a significant tumor regression through photothermal therapy and immune checkpoint blockade, leading to a durable antitumor-immune response. Overall, "Three-in-one" immunotherapeutic photo-activable nanoparticles have the potential to be beneficial for a targeted combinatorial treatment approach for TNBC | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Vasukutty, Arathy |e verfasserin |4 aut | |
| 700 | 1 | |a Baek, Seonguk |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jae Young |e verfasserin |4 aut | |
| 700 | 1 | |a Park, In-Kyu |e verfasserin |4 aut | |
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