Gold Nanoparticles Enhance the Ability of Radiotherapy to Induce Immunogenic Cell Death in Glioblastoma

Abstract

Chen He,1– 3,* Huiyan Ding,4,* Lubo Li,5 Jing Chen,6 Xiaofei Mo,1– 3 Yinan Ding,4 Wenjing Chen,4 Qiusha Tang,4 Yuetao Wang1– 3 1Department of Nuclear Medicine, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou, Jiangsu Province, People’s Republic of China; 3Changzhou Clinical Medical Center, Changzhou, Jiangsu, People’s Republic of China; 4Medical School of Southeast University, Nanjing, People’s Republic of China; 5The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 6Taikang Xianlin Drum Tower Hospital, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiusha Tang; Yuetao Wang, Email [email protected]; [email protected]: Radiation therapy (RT) is commonly used to treat glioblastoma, but its immunomodulatory effect on tumors, through mechanisms such as immunogenic cell death (ICD), is relatively weak. Gold nanoparticles (AuNPs) have been suggested as potential radio-sensitizers, but it is unclear if they can enhance radiation-induced ICD. This study aimed to investigate the potential of AuNPs to improve the effectiveness of radiation-induced ICD.Methods: G422 cells were treated with a combination of AuNPs and RT to induce cell death. Various assays were conducted to assess cell death, surface expression of CRT, and release of HMGB1 and ATP. In vitro co-culture experiments with bone marrow-derived dendritic cells (BMDCs) were performed to analyze the immunogenicity of dying cancer cells. Flow cytometry was used to measure the maturation rate of BMDCs. An in vivo mouse tumor prophylactic vaccination model was employed to assess immunogenicity.Results: The study findings presented here confirm that the combination of radiotherapy (RT) with AuNPs can induce a stronger ICD effect on glioblastoma cells compared to using RT alone. Specifically, treatment with AuNPs combined with RT resulted in the emission of crucial damage-associated molecular patterns (DAMPs) such as CRT, HMGB1 (479.41± 165.34pg/mL vs 216.04± 178.16 pg/mL, *P< 0.05) and ATP (The release of ATP in the AuNPs + RT group was 1.2 times higher than in the RT group, *P< 0.05). The proportion of BMDC maturation rate was higher in the group treated with AuNPs and RT compared to the group treated with RT alone. (32.53± 0.52% vs 25.03± 0.28%,***P < 0.001). In the tumor vaccine experiment, dying tumor cells treated with AuNPs and RT effectively inhibited tumor growth in mice when exposed to living tumor cells.Conclusion: These results indicate that AuNPs have the ability to enhance RT-induced ICD.Keywords: Immunogenic cell death, Gold nanoparticles, Radiation therapy, Glioblastoma

Keywords

• immunogenic cell death
• gold nanoparticles
• radiation therapy
• glioblastoma