Stimulator of Interferon Genes-Activated Biomimetic Dendritic Cell Nanovaccine as a Chemotherapeutic Booster to Enhance Systemic Fibrosarcoma Treatment

Fibrosarcoma, a malignant mesenchymal tumor, is characterized by aggressive invasiveness and a high recurrence rate, leading to poor prognosis. Anthracycline drugs, such as doxorubicin (DOX), represent the frontline chemotherapy for fibrosarcoma, but often exhibit suboptimal efficacy. Recently, expl...

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Veröffentlicht in:ACS nano 2024-09, Vol.18 (35), p.24219-24235
Hauptverfasser: Wang, Zhao, Miao, Fenglin, Gu, Lingwei, Zhang, Ruyi, Ma, Yuan, Li, Ying, Zheng, Jialiang, Lin, Zhenhang, Gao, Yilai, Huang, Liyong, Shen, Ye, Wu, Ting, Luo, Fanghong, Li, Wengang
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container_end_page 24235
container_issue 35
container_start_page 24219
container_title ACS nano
container_volume 18
creator Wang, Zhao
Miao, Fenglin
Gu, Lingwei
Zhang, Ruyi
Ma, Yuan
Li, Ying
Zheng, Jialiang
Lin, Zhenhang
Gao, Yilai
Huang, Liyong
Shen, Ye
Wu, Ting
Luo, Fanghong
Li, Wengang
description Fibrosarcoma, a malignant mesenchymal tumor, is characterized by aggressive invasiveness and a high recurrence rate, leading to poor prognosis. Anthracycline drugs, such as doxorubicin (DOX), represent the frontline chemotherapy for fibrosarcoma, but often exhibit suboptimal efficacy. Recently, exploiting the stimulator of interferon genes (STING)-mediated innate immunity has emerged as a hopeful strategy for cancer treatment. Integrating chemotherapy with immunomodulators in chemo-immunotherapy has shown potential for enhancing treatment outcomes. Herein, we introduce an advanced dendritic cell (DC) nanovaccine, cGAMP@PLGA@CRTM (GP@CRTM), combined with low-dose DOX to enhance fibrosarcoma chemo-immunotherapy. The nanovaccine consists of poly­(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating the STING agonist 2,3-cGAMP (cGAMP@PLGA, GP) as its core, and a calreticulin (CRT) high-expressing fibrosarcoma cell membrane (CRTM) as the shell. Exposing CRT on the vaccine surface aids in recruiting DCs and stimulating uptake, facilitating efficient simultaneous delivery of STING agonists and tumor antigens to DCs. This dual delivery method effectively activates the STING pathway in DCs, triggering sustained immune stimulation. Simultaneously, low-dose DOX reduces chemotherapy-related side effects, directly kills a subset of tumor cells, and increases tumor immunogenicity, thus further amplifying immune therapeutic performance. Hence, these findings demonstrate the potential of DC nanovaccine GP@CRTM as a booster for chemotherapy. Synergistically combining low-dose DOX with the DC nanovaccine emerges as a powerful chemo-immunotherapy strategy, optimizing systemic fibrosarcoma therapy.
doi_str_mv 10.1021/acsnano.4c05657
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Anthracycline drugs, such as doxorubicin (DOX), represent the frontline chemotherapy for fibrosarcoma, but often exhibit suboptimal efficacy. Recently, exploiting the stimulator of interferon genes (STING)-mediated innate immunity has emerged as a hopeful strategy for cancer treatment. Integrating chemotherapy with immunomodulators in chemo-immunotherapy has shown potential for enhancing treatment outcomes. Herein, we introduce an advanced dendritic cell (DC) nanovaccine, cGAMP@PLGA@CRTM (GP@CRTM), combined with low-dose DOX to enhance fibrosarcoma chemo-immunotherapy. The nanovaccine consists of poly­(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating the STING agonist 2,3-cGAMP (cGAMP@PLGA, GP) as its core, and a calreticulin (CRT) high-expressing fibrosarcoma cell membrane (CRTM) as the shell. Exposing CRT on the vaccine surface aids in recruiting DCs and stimulating uptake, facilitating efficient simultaneous delivery of STING agonists and tumor antigens to DCs. This dual delivery method effectively activates the STING pathway in DCs, triggering sustained immune stimulation. Simultaneously, low-dose DOX reduces chemotherapy-related side effects, directly kills a subset of tumor cells, and increases tumor immunogenicity, thus further amplifying immune therapeutic performance. Hence, these findings demonstrate the potential of DC nanovaccine GP@CRTM as a booster for chemotherapy. 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subjects Animals
Biomimetic Materials - chemistry
Biomimetic Materials - pharmacology
Calreticulin - metabolism
Cancer Vaccines - immunology
Cell Line, Tumor
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - metabolism
Doxorubicin - chemistry
Doxorubicin - pharmacology
Fibrosarcoma - drug therapy
Fibrosarcoma - immunology
Fibrosarcoma - pathology
Fibrosarcoma - therapy
Humans
Immunotherapy
Membrane Proteins - metabolism
Mice
Mice, Inbred C57BL
Nanoparticles - chemistry
Nanovaccines
Nucleotides, Cyclic - chemistry
Nucleotides, Cyclic - pharmacology
Polylactic Acid-Polyglycolic Acid Copolymer - chemistry
title Stimulator of Interferon Genes-Activated Biomimetic Dendritic Cell Nanovaccine as a Chemotherapeutic Booster to Enhance Systemic Fibrosarcoma Treatment
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