title: A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy.
abstract: 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.
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.
authors.forename: Chuangnian
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Basic Nursing T&R Section, School of Nursing, Qingdao University , Qingdao, Shandong Province 26000, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.
authors.forename: Gaona
authors.initials: G
authors.lastname: Shi
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Song
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.
authors.forename: Shengbin
authors.initials: S
authors.lastname: Shi
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.
authors.forename: Xiuyuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.|Department of Biomedical Engineering, University of Minnesota , 7-105 Hasselmo Hall, 312 Church Street South East, Minneapolis, Minnesota 55455, United States.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.|State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University , Tianjin, 300071, China.
authors.forename: Deling
authors.identifier: 0000-0002-5520-0769
authors.initials: D
authors.lastname: Kong
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin, 300192, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002734:Chlorophyll; D026082:Singlet Oxygen; D011094:Polyethyleneimine; C032623:pheophorbide a
keywords: antigen delivery; cross-presentation; endosome escape; immunotherapy; photochemical internalization