Cancer Radiosensitization Nanoagent to Activate cGAS-STING Pathway for Molecular Imaging Guided Synergistic Radio/Chemo/Immunotherapy.
Adv Healthc Mater
; 13(14): e2303626, 2024 06.
Article
em En
| MEDLINE
| ID: mdl-38387885
ABSTRACT
Immunotherapy has emerged as an innovative strategy with the potential to improve outcomes in cancer patients. Recent evidence indicates that radiation-induced DNA damage can activate the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to enhance the antitumor immune response. Even so, only a small fraction of patients currently benefits from radioimmunotherapy due to the radioresistance and the inadequate activation of the cGAS-STING pathway. Herein, this work integrates hafnium oxide (HfO2) nanoparticles (radiosensitizer) and 7-Ethyl-10-hydroxycamptothecin (SN38, chemotherapy drug, STING agonist) into a polydopamine (PDA)-coated core-shell nanoplatform (HfO2@PDA/Fe/SN38) to achieve synergistic chemoradiotherapy and immunotherapy. The co-delivery of HfO2/SN38 greatly enhances radiotherapy efficacy by effectively activating the cGAS-STING pathway, which then triggers dendritic cells maturation and CD8+ T cells recruitment. Consequently, the growth of both primary and abscopal tumors in tumor-bearing mice is efficiently inhibited. Moreover, the HfO2@PDA/Fe/SN38 complexes exhibit favorable magnetic resonance imaging (MRI)/photoacoustic (PA) bimodal molecular imaging properties. In summary, these developed multifunctional complexes have the potential to intensify immune activation to realize simultaneous cancer Radio/Chemo/Immunotherapy for clinical translation.
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Base de dados:
MEDLINE
Assunto principal:
Nanopartículas
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Imunoterapia
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Proteínas de Membrana
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Nucleotidiltransferases
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article