title: Upconversion nanoparticle-mediated photodynamic therapy induces THP-1 macrophage apoptosis via ROS bursts and activation of the mitochondrial caspase pathway.
abstract: Atherosclerosis (AS) is the most vital cardiovascular disease, which poses a great threat to human health. Macrophages play an important role in the progression of AS. Photodynamic therapy (PDT) has emerged as a useful therapeutic modality not only in the treatment of cancer but also in the treatment of AS. The purpose of this study was to determine the molecular mechanisms underlying the activity of PDT, using mesoporous-silica-coated upconversion fluorescent nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) in the induction of apoptosis in THP-1 macrophages. Here, we investigated the ability of UCNPs-Ce6-mediated PDT to induce THP-1 macrophage apoptosis by facilitating the induction of reactive oxygen species (ROS) and regulation of mitochondrial permeability transition pore (MPTP) to depolarize mitochondrial membrane potential (MMP). Both Bax translocation and the release of cytochrome C were examined using immunofluorescence and Western blotting. Our results indicated that the levels of ROS were significantly increased in the PDT group, resulting in both MPTP opening and MMP depolarization, which led to apoptosis. In addition, immunofluorescence and Western blotting revealed that PDT induced both Bax translocation and the release of cytochrome C, as well as upregulation of cleaved caspase-9, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase. Therefore, we demonstrated that UCNPs-Ce6-mediated PDT induces apoptosis in THP-1 macrophages via ROS bursts. The proapoptotic factor Bax subsequently translocates from the cytosol to the mitochondria, resulting in the MPTP opening and cytochrome C release. This study demonstrated the great potential of UCNPs-Ce6-mediated PDT in the treatment of AS.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Materials Physics and Chemistry Department, Harbin Institute of Technology, Harbin, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Longbin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Li
authors.affiliation: Blood Transfusion Department, Jining No 1 People's Hospital, Jining, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Jiayuan
authors.initials: J
authors.lastname: Kou
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Zhongni
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: Laboratory of Sono- and Photo-theranostic Technologies, Harbin Institute of Technology, Harbin, People's Republic of China ; Materials Research Institute, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China ; Division of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Materials Physics and Chemistry Department, Harbin Institute of Technology, Harbin, People's Republic of China.
authors.forename: You
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Liming
authors.initials: L
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D002735:Chlorophyllides; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011166:Porphyrins / Q000737:chemistry* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D002735:Chlorophyllides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; C062985:phytochlorin; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases
keywords: apoptosis; atherosclerosis; fluorescent nanoparticles; macrophages; photodynamic therapy; reactive oxygen species