title: Ex vivo generation of functional immune cells by mitochondria-targeted photosensitization of cancer cells.
abstract: Stimulating the immune system for potent immune therapy against cancer is potentially a revolutionary method to eradicate cancer. Tumors stimulated with photosensitizers (PSs) not only kill cancer cells but also help to boost the immune system. We recently reported that tumor-associated antigens (TAAs) generated by delivery of a mitochondria-acting PS zinc phthalocyanine (ZnPc) to MCF-7 breast cancer cells followed by laser irradiation can lead to ex vivo stimulation of mouse bone marrow-derived dendritic cells (BMDCs). The antigens generated from the breast cancer cells were also found to cause significant DC maturation and the activated DCs were able to stimulate T cells to cytotoxic CD8(+) T cells. In this protocol, we describe methods to engineer a mitochondria-targeted biodegradable nanoparticle (NP) formulation, T-ZnPc-NPs for delivery of ZnPc to the mitochondria of MCF-7 cells, subsequent photodynamic therapy (PDT) using a long wavelength laser irradiation to produce TAAs, DC stimulation by the TAAs to secrete interferon-gamma (IFN-γ), and matured DC-driven T-cell activation.
authors: NanoTherapeutics Research Laboratory, Department of Chemistry, University of Georgia, Athens, GA, 30602, USA.
authors: Sean
authors: S
authors: Marrache
authors: Smanla
authors: S
authors: Tundup
authors: Donald A
authors: DA
authors: Harn
authors: Shanta
authors: S
authors: Dhar
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000528:radiation effects; D058726:Nanoconjugates / Q000737:chemistry*; D010778:Photochemotherapy; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D058726:Nanoconjugates; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols