Dendritic cells reprogrammed by CEA messenger RNA loaded multi-functional silica nanospheres for imaging-guided cancer immunotherapy

• Published in: Biomaterials science Vol. 8; no. 11; pp. 326 - 331
• Main Authors: Hu, Yue, Tang, Yuyin, Zhang, Xiao-Jing, Yang, Xiao-Tong, Tang, Ying-Ying, Li, Su, Hu, Linyu, Chen, Peng, Zhu, Dong
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 07.06.2020
• Subjects: Animals; Antigens; Assaying; biocompatible materials; Cancer; cancer therapy; Carcinoembryonic Antigen - genetics; cell proliferation; Cytotoxicity; dendritic cells; Dendritic Cells - metabolism; Fluorescence; Homing; immune response; Immune system; Immunotherapy; Infrared imaging; lymph; Lymphatic system; Lymphocytes; Melanoma, Experimental - diagnostic imaging; Melanoma, Experimental - metabolism; Melanoma, Experimental - therapy; messenger RNA; Mice, Inbred C57BL; Nanoparticles; Nanospheres; Nanospheres - administration & dosage; neoplasms; Nodes; Optical Imaging; Optimization; Quantum dots; RNA, Messenger - administration & dosage; silica; Silicon dioxide; Silicon Dioxide - administration & dosage; T-lymphocytes
• ISSN: 2047-4830; 2047-4849; 2047-4849
• DOI: 10.1039/d0bm00395f

The application and understanding of dendritic cell (DC) based immune cancer therapy are largely hindered by insufficient or improper presentation of antigens and the inability to track the homing of reprogrammed DCs to draining lymph nodes in real-time. To tackle these challenges, multi-functional and hierarchically structured silica nanospheres are rationally designed and fabricated, which encapsulate quantum dots to permit near infrared deep tissue imaging and are loaded with carcinoembryonic antigen messenger RNA (CEAmRNA) to enable stable and abundant antigen expression in DCs. After being injected into animals and inducing an antigen-specific immune response, the homing process of reprogrammed labelled DCs from peripheral tissues to draining lymph nodes can be simultaneously and precisely tracked. Significant inhibition of tumor growth is achieved via strong antigen-specific immune responses including induced DC maturation, enhanced T cell proliferation and cytotoxic T lymphocyte (CTL)-mediated responses. Both in vitro and in vivo experiments demonstrate the high effectiveness of this new strategy of imaging-guided cancer immunotherapy by using reprogrammed DCs as immunotherapeutic and tracking agents. Multi-functional and hierarchically structured silica nanospheres are rationally designed and fabricated, which encapsulate quantum dots to permit near infrared deep tissue imaging and are loaded with carcinoembryonic antigen messenger RNA (CEAmRNA) to enable stable and abundant antigen expression in DCs.