title: A Photosensitizer-Loaded DNA Origami Nanosystem for Photodynamic Therapy.
abstract: Photodynamic therapy (PDT) offers an alternative for cancer treatment by using ultraviolet or visible light in the presence of a photosensitizer and molecular oxygen, which can produce highly reactive oxygen species that ultimately leading to the ablation of tumor cells by multifactorial mechanisms. However, this technique is limited by the penetration depth of incident light, the hypoxic environment of solid tumors, and the vulnerability of photobleaching reduces the efficiency of many imaging agents. In this work, we reported a cellular level dual-functional imaging and PDT nanosystem BMEPC-loaded DNA origami for photodynamic therapy with high efficiency and stable photoreactive property. The carbazole derivative BMEPC is a one- and two-photon imaging agent and photosensitizer with large two-photon absorption cross section, which can be fully excited by near-infrared light, and is also capable of destroying targets under anaerobic condition by generating reactive intermediates of Type I photodynamic reactions. However, the application of BMEPC was restricted by its poor solubility in aqueous environment and its aggregation caused quenching. We observed BMEPC-loaded DNA origami effectively reduced the photobleaching of BMEPC within cells. Upon binding to DNA origami, the intramolecular rotation of BMEPC became proper restricted, which intensify fluorescence emission and radicals production when being excited. After the BMEPC-loaded DNA origami are taken up by tumor cells, upon irradiation, BMEPC could generate free radicals and be released due to DNA photocleavage as well as the following partially degradation. Apoptosis was then induced by the generation of free radicals. This functional nanosystem provides an insight into the design of photosensitizer-loaded DNA origami for effective intracellular imaging and photodynamic therapy.
authors.affiliation: Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.affiliation: Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Xue
authors.affiliation: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Song
authors.affiliation: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Luru
authors.initials: L
authors.lastname: Dai
authors.affiliation: Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Chunqiu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Shubin
authors.initials: S
authors.lastname: Jin
authors.affiliation: Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Keni
authors.initials: K
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Baoquan
authors.initials: B
authors.lastname: Ding
authors.affiliation: Fu Jen Catholic University , Taipei 24205, Taiwan.|Laboratory of Molecular Imaging, Department of Radiology, Howard University , Washington, DC 20060, United States.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Wang
authors.affiliation: Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology , Beijing 100190, China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
mesh_terms: D001940:Breast / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002227:Carbazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D004247:DNA / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D038761:Photobleaching; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D002227:Carbazoles; D004337:Drug Carriers; D017319:Photosensitizing Agents; D004247:DNA
keywords: DNA origami; carbazole derivative photosensitizer; dual-functionality; intracellular imaging; photodynamic therapy