title: Highly efficient hierarchical micelles integrating photothermal therapy and singlet oxygen-synergized chemotherapy for cancer eradication.
abstract: It is highly desirable to develop theranostic nanoparticles for achieving cancer imaging with enhanced contrast and simultaneously multimodal synergistic therapy. Herein, we report a theranostic micelle system hierarchically assembling cyanine dye (indocyanine green) and chemotherapeutic compound (doxorubicin) (I/D-Micelles) as a novel theranostic platform with high drug loading, good stability and enhanced cellular uptake via clathrin-mediated endocytosis. I/D-Micelles exhibit the multiple functionalities including near-infrared fluorescence (NIRF), hyperthermia and intracellular singlet oxygen from indocyanine green, and simultaneous cytotoxicity from doxorubicin. Upon photoirradiation, I/D-Micelles can induce NIRF imaging, acute photothermal therapy via hyperthermia and simultaneous synergistic chemotherapy via singlet oxygen-triggered disruption of lysosomal membranes, eventually leading to enhanced NIRF imaging and superior tumor eradication without any re-growth. Our results suggest that the hierarchical micelles can act as a superior theranostic platform for cancer imaging and multimodal synergistic therapy.
authors.affiliation: 1. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Wan
authors.affiliation: 1. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Huajian
authors.initials: H
authors.lastname: Mao
authors.affiliation: 1. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Guo
authors.affiliation: 1. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.affiliation: 1. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Zhu
authors.affiliation: 1. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.affiliation: 1. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: 2. Radiology Department, Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
authors.forename: Junkang
authors.initials: J
authors.lastname: Shen
authors.affiliation: 2. Radiology Department, Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: 2. Radiology Department, Second Affiliated Hospital, Soochow University, Suzhou 215004, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: 3. School for Radiological & Interdisciplinary sciences (RAD-X), and School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Ge
authors.affiliation: 4. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health Bethesda, Maryland 20892, United States.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: 5. College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
authors.affiliation: 6. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: 1. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China ; 3. School for Radiological & Interdisciplinary sciences (RAD-X), and School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China.
authors.forename: Huabing
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D003131:Combined Modality Therapy; D003952:Diagnostic Imaging / Q000379:methods; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D005453:Fluorescence; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007208:Indocyanine Green / Q000737:chemistry; D008247:Lysosomes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D009374:Neoplasms, Experimental / Q000628:therapy; D010789:Phototherapy / Q000379:methods*; D011817:Rabbits; D026082:Singlet Oxygen / Q000627:therapeutic use*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D026082:Singlet Oxygen; D004317:Doxorubicin; D007208:Indocyanine Green
keywords: Cancer eradication; Hierarchical micelles; Photothermal therapy; Singlet oxygen; Synergistic therapy