title: Cellular and Mitochondrial Dual-Targeted Organic Dots with Aggregation-Induced Emission Characteristics for Image-Guided Photodynamic Therapy.
abstract: Targeted delivery of drugs toward mitochondria of specific cancer cells dramatically improves therapy efficiencies especially for photodynamic therapy (PDT), as reactive oxygen species (ROS) are short in lifetime and small in radius of action. Different from chemical modification, nanotechnology has been serving as a simple and nonchemical approach to deliver drugs to cells of interest or specific organelles, such as mitochondria, but there have been limited examples of dual-targeted delivery for both cells and mitochondria. Here, cellular and mitochondrial dual-targeted organic dots for image-guided PDT are reported based on a fluorogen with aggregation-induced emission (AIEgen) characteristics. The AIEgen possesses enhanced red fluorescence and efficient ROS production in aggregated states. The AIE dot surfaces are functionalized with folate and triphenylphosphine, which can selectively internalize into folate-receptor (FR) positive cancer cells, and subsequently accumulate at mitochondria. The direct ROS generation at mitochondria sites is found to depolarize mitochondrial membrane, affect cell migration, and lead to cell apoptosis and death with enhanced PDT effects as compared to ROS generated randomly in cytoplasm. This report demonstrates a simple and general nanocarrier approach for cellular and mitochondrial dual-targeted PDT, which opens new opportunities for dual-targeted delivery and therapy.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.|Environmental Research Institute, National University of Singapore, Singapore, 117411, Singapore.
authors.forename: Guangxue
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Chemistry and Division of Biomedical Engineering, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.
authors.forename: Qinglian
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Chemistry and Division of Biomedical Engineering, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.|SCUT-HKUST Joint Research Laboratory, Guangdong Innovative Research Team, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou, 510640, China.
authors.forename: Ben Zhong
authors.initials: BZ
authors.lastname: Tang
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.|Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), Singapore, 117602, Singapore.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005453:Fluorescence; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D041681:NIH 3T3 Cells; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D005492:Folic Acid
keywords: aggregation-induced emission (AIE); cancer cell targeting; drug delivery; mitochondrial imaging; photodynamic therapy