In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8+ T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape activity and near-infrared imaging capability was prepared. A model antigen ovalbumin (OVA) was then complexed with PheoA-PEI to form PheoA-PEI/OVA nanoparticles (PheoA-PEI/OVA NPs) that are responsive to light. Flow cytometry analysis revealed increased endocytosis in a murine dendritic cell line (DC2.4) that was treated with PheoA-PEI/OVA NPs compared to free OVA. Generation of reactive oxygen species (ROS) in DC2.4 cells was also confirmed quantitatively and qualitatively using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). Confocal laser scanning microscopy (CLSM) further demonstrated that the PheoA-PEI/OVA NPs enhanced cytosolic antigen release after light stimulation. Moreover, PheoA-PEI/OVA NP treated DC2.4 cells exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro after light irradiation, substantially increased compared to those treated with free OVA. Consistently, in vivo results revealed upregulation of CD3+CD8+T lymphocytes in tumors of mice treated with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. The activated T cell response is partly responsible for the inhibitory effect on E.G7 tumor growth in mice immunized with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. Our results demonstrate the feasibility to enhance antigen-specific CD8+ T cell immune response by light-responsive nanoparticle-based vaccine delivery for cancer immunotherapy.
Bibliographical noteFunding Information:
This work was financially supported by the National Natural Science Foundation of China (21604095, 31300732, 51373199 31400833, 1670977), China Postdoctoral Science Foundation (2015M580066), Program for Innovative Research Team in Peking Union Medical College, CAMS Initiative for Innovative Medicine (2016-I2M-3-022), and the Open Fund of Key Laboratory of Functional Polymer Materials, Ministry of Education, Nankai University (201606).
© 2017 American Chemical Society.
Copyright 2017 Elsevier B.V., All rights reserved.
- antigen delivery
- endosome escape
- photochemical internalization