Journal
ADVANCED HEALTHCARE MATERIALS
Volume 4, Issue 17, Pages 2667-2676Publisher
WILEY
DOI: 10.1002/adhm.201500431
Keywords
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Funding
- Singapore National Research Foundation [R279-000-444-281]
- SMART [R279-000-378-592]
- Economic Development Board (Singapore-Peking-Oxford Research Enterprise) [COY-15-EWI-RCFSA/N197-1]
- Institute of Materials Research and Engineering of Singapore [IMRE/14-8P1110]
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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.
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