title: Ex vivo programming of dendritic cells by mitochondria-targeted nanoparticles to produce interferon-gamma for cancer immunotherapy.
abstract: One of the limitations for clinical applications of dendritic cell (DC)-based cancer immunotherapy is the low potency in generating tumor antigen specific T cell responses. We examined the immunotherapeutic potential of a mitochondria-targeted nanoparticle (NP) based on a biodegradable polymer and zinc phthalocyanine (ZnPc) photosensitizer (T-ZnPc-NPs). Here, we report that tumor antigens generated from treatment of breast cancer cells with T-ZnPc-NPs upon light stimulation activate DCs to produce high levels of interferon-gamma, an important cytokine considered as a product of T and natural killer cells. The remarkable ex vivo DC stimulation ability of this tumor cell supernatant is a result of an interleukin (IL)-12/IL-18 autocrine effect. These findings contribute to the understanding of how in situ light activation amplifies the host immune responses when NPs deliver the photosensitizer to the mitochondria and open up the possibility of using mitochondria-targeted-NP-treated, light-activated cancer cell supernatants as possible vaccines.
authors.affiliation: NanoTherapeutics Research Laboratory, Department of Chemistry, University of Georgia, Athens, Georgia 30602, United States.
authors.forename: Sean
authors.initials: S
authors.lastname: Marrache
authors.forename: Smanla
authors.initials: S
authors.lastname: Tundup
authors.forename: Donald A
authors.initials: DA
authors.lastname: Harn
authors.forename: Shanta
authors.initials: S
authors.lastname: Dhar
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry; D017209:Apoptosis; D001672:Biocompatible Materials / Q000737:chemistry; D019496:Cancer Vaccines / Q000737:chemistry; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007211:Indoles / Q000737:chemistry; D007371:Interferon-gamma / Q000378:metabolism*; D054833:Isoindoles; D061986:MCF-7 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D009336:Necrosis; D009369:Neoplasms / Q000628:therapy*; D009942:Organometallic Compounds / Q000737:chemistry; D017319:Photosensitizing Agents / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D017967:Zinc Compounds
chemical_list: D000951:Antigens, Neoplasm; D001672:Biocompatible Materials; D019496:Cancer Vaccines; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011108:Polymers; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D007371:Interferon-gamma