Phototherapy and anti-GITR antibody-based therapy synergistically reinvigorate immunogenic cell death and reject established cancers. (February 2021)

• Record Type: Journal Article
• Authors: Sun, Qi; Yang, Zhenzhen; Lin, Meng; Peng, Yiwei; Wang, Rudong; Du, Yitian; Zhou, Yu; Li, Jiajia; Qi, Xianrong
• Is Part Of: Biomaterials. Volume 269(2021)
• Publication Date: 2021-02
• Subjects: Phototherapy -- Anti-GITR antibody -- Immunotherapy -- Immunogenic cell death -- Tumor immune suppression; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2020.120648
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Phototherapy and immunogenic cell death (ICD) are powerful strategies to fight cancer. However, their therapeutic outcomes are diminished by immunosuppressive and hypoxia microenvironment. Herein, a photo-based, immunomodulating and hypoxia-alleviated nanosystem, PDA-ICG@CAT-DTA-1, is proposed to achieve the synergism between phototherapy and immunotherapy. Catalase (CAT) and anti-GITR antibody (DTA-1) are loaded to photothermal agent and photosensitizer composed PDA-ICG nanoparticles. The PDA-ICG@CAT-DTA-1 exhibits intrinsic local hyperthermia and enhanced ROS generation in tumor, and abrogates tumor immune suppression. It results in reduction of intratumoral FOXP3 + regulatory T cells (4.3-fold) and increase of CD4 + effector T cells (1.5-fold) compare with the control, and promotes damage associated molecular patterns generation to reinvigorate ICD effect. The potent antitumor of PDA-ICG@CAT-DTA-1 is proved in 4T1 bilateral tumor-bearing mice, with inhibition ratio of 95.1% for primary cancers and 68.7% for abscopal cancers. Our findings highlight great promise of the constructed versatility nanosystem to fix bottlenecks for cancer therapy. Graphical abstract: Image 1