Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy

Abstract The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cel...

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Main Authors: Huating Huang, Jing Fu, Hulinyue Peng, Yuanyuan He, Aqian Chang, Huizhong Zhang, Yang Hao, Xiaohan Xu, Shiman Li, Jingxia Zhao, Jian Ni, Xiaoxv Dong
Format: Article
Language:English
Published: BMC 2024-10-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-024-02887-6
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author Huating Huang
Jing Fu
Hulinyue Peng
Yuanyuan He
Aqian Chang
Huizhong Zhang
Yang Hao
Xiaohan Xu
Shiman Li
Jingxia Zhao
Jian Ni
Xiaoxv Dong
author_facet Huating Huang
Jing Fu
Hulinyue Peng
Yuanyuan He
Aqian Chang
Huizhong Zhang
Yang Hao
Xiaohan Xu
Shiman Li
Jingxia Zhao
Jian Ni
Xiaoxv Dong
author_sort Huating Huang
collection DOAJ
description Abstract The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cells. Polyphyllin II (PPII), the major active component of Rhizoma Paridis, has been demonstrated for the first time to induce pyroptosis in tumor cells, while IR780 is activated by 808 nm laser to transform light energy into heat energy, effectively eliminating tumor cells. However, both PPII and IR780 are afflicted with challenges such as low solubility and poor targeting, significantly limiting their utilization. To address these problems, the pyroptosis inducer PPII and photosensitizer IR780 were co-loaded in PLGA nanoparticles by precipitation method, and the aptamer AS1411 was modified on the surface of nanoparticles to construct the targeting nanoparticles (Apt/PPII/IR780-NPs). The nanoparticles exhibit a pH/NIR dual-response intelligent release feature, which realizes the targeted and controlled release of drugs in tumor site. Furthermore, it can rapidly release PPII to induce cell pyroptosis under laser irradiation, combining with IR780-based photothermal therapy exert a significant synergistic anti-tumor effect in vitro and in vivo. This process not only promotes maturation of DCs and activates effector T cells, thereby initiating adaptive immunity, but also generates enduring and effective immune memory. In addition, Apt/PPII/IR780-NPs significantly improved the Anti-PD-1 efficacy. In summary, chemo-photothermal therapy based on Apt/PPII/IR780-NPs can significantly enhance tumor ICD, which provides a promising new strategy for HCC immunotherapy.
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spelling doaj-art-66623a52187242bbbbef73051edd7d2d2025-08-20T02:11:54ZengBMCJournal of Nanobiotechnology1477-31552024-10-0122112110.1186/s12951-024-02887-6Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapyHuating Huang0Jing Fu1Hulinyue Peng2Yuanyuan He3Aqian Chang4Huizhong Zhang5Yang Hao6Xiaohan Xu7Shiman Li8Jingxia Zhao9Jian Ni10Xiaoxv Dong11School of Chinese Material Medica, Beijing University of Chinese MedicineBeijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical UniversitySchool of Chinese Material Medica, Beijing University of Chinese MedicineDepartment of Radiology, Leiden University Medical CenterSchool of Chinese Material Medica, Beijing University of Chinese MedicineSchool of Chinese Material Medica, Beijing University of Chinese MedicineDepartment of Laboratory Animals, College of Animal Sciences, Jilin UniversitySchool of Chinese Material Medica, Beijing University of Chinese MedicineSchool of Chinese Material Medica, Beijing University of Chinese MedicineBeijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical UniversitySchool of Chinese Material Medica, Beijing University of Chinese MedicineSchool of Chinese Material Medica, Beijing University of Chinese MedicineAbstract The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cells. Polyphyllin II (PPII), the major active component of Rhizoma Paridis, has been demonstrated for the first time to induce pyroptosis in tumor cells, while IR780 is activated by 808 nm laser to transform light energy into heat energy, effectively eliminating tumor cells. However, both PPII and IR780 are afflicted with challenges such as low solubility and poor targeting, significantly limiting their utilization. To address these problems, the pyroptosis inducer PPII and photosensitizer IR780 were co-loaded in PLGA nanoparticles by precipitation method, and the aptamer AS1411 was modified on the surface of nanoparticles to construct the targeting nanoparticles (Apt/PPII/IR780-NPs). The nanoparticles exhibit a pH/NIR dual-response intelligent release feature, which realizes the targeted and controlled release of drugs in tumor site. Furthermore, it can rapidly release PPII to induce cell pyroptosis under laser irradiation, combining with IR780-based photothermal therapy exert a significant synergistic anti-tumor effect in vitro and in vivo. This process not only promotes maturation of DCs and activates effector T cells, thereby initiating adaptive immunity, but also generates enduring and effective immune memory. In addition, Apt/PPII/IR780-NPs significantly improved the Anti-PD-1 efficacy. In summary, chemo-photothermal therapy based on Apt/PPII/IR780-NPs can significantly enhance tumor ICD, which provides a promising new strategy for HCC immunotherapy.https://doi.org/10.1186/s12951-024-02887-6PyroptosisPhotothermalAptamerImmunotherapy
spellingShingle Huating Huang
Jing Fu
Hulinyue Peng
Yuanyuan He
Aqian Chang
Huizhong Zhang
Yang Hao
Xiaohan Xu
Shiman Li
Jingxia Zhao
Jian Ni
Xiaoxv Dong
Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy
Journal of Nanobiotechnology
Pyroptosis
Photothermal
Aptamer
Immunotherapy
title Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy
title_full Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy
title_fullStr Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy
title_full_unstemmed Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy
title_short Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy
title_sort co delivery of polyphyllin ii and ir780 plga nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy
topic Pyroptosis
Photothermal
Aptamer
Immunotherapy
url https://doi.org/10.1186/s12951-024-02887-6
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