Nano-assemblies of J-aggregates based on a NIR dye as a multifunctional drug carrier for combination cancer therapy |
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| Affiliation: | 1. Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, China;2. Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China;3. Laboratory of Physical Biology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China;1. Materials Science Program, University of Wisconsin–Madison, WI, USA;2. Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials Laboratory (FUNSOM), Soochow University, Suzhou, Jiangsu, China;3. Department of Radiology, University of Wisconsin–Madison, WI, USA;4. Department of Medical Physics, University of Wisconsin–Madison, WI, USA;5. University of Wisconsin Carbone Cancer Center, Madison, WI, USA;1. Center for Molecular Imaging, Department of Radiology, University of Michigan – Ann Arbor, MI 48109-2200, United States;2. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China;3. Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials Laboratory (FUNSOM), Soochow University, Suzhou, Jiangsu 215123, China;4. Department of Chemistry, University of Michigan – Ann Arbor, MI 48109-1055, United States;5. University of Michigan Comprehensive Cancer Center, MI 48109-0944, United States;1. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China;2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidad, Taipa, Macau, China;1. Department of Medical Physics, University of Wisconsin – Madison, Madison, WI 53705, USA;2. Department of Radiology, University of Wisconsin – Madison, WI 53705, USA;3. Department of Molecular Medicine and Biopharmaceutical Sciences, Department of Nuclear Medicine, Seoul National University, Seoul 110-744, South Korea;4. Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices Laboratory, Soochow University Suzhou, Jiangsu 215123, China;5. Department of Surgery, University of California-Davis, Sacramento, CA 95817, USA;6. University of Wisconsin Carbone Cancer Center, Madison, WI 53705, USA;1. Institute for Pediatric Research, Affiliated Children''s Hospital, Soochow University, Suzhou, Jiangsu 215025, China;2. Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, China;3. Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province, State Key Laboratory Incubation Base, Soochow University, Suzhou, Jiangsu 215007, China;4. Department of Academic Surgery, University College Cork, Cork University Hospital, Cork, Ireland |
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| Abstract: | The combination of chemotherapy with photothermal therapy, which may lead to improved therapeutic efficacies and reduced side effects of conventional chemotherapy, would require safe drug delivery systems (DDSs) with strong near-infrared (NIR) absorbance, efficient drug loading, and effective tumor homing ability. Herein, we fabricate nano-assemblies containing J-aggregates of a NIR dye, IR825, for drug delivery and combined photothermal & chemotherapy of cancer. It is found that IR825 could be complexed with a low-molecular-weight cationic polymer polyethylenimine (PEI), forming IR825@PEI J-aggregates with greatly enhanced NIR absorbance red-shifted to 915 nm. Those nano-assemblies of J-aggregates are further modified with polyethylene glycol (PEG), obtaining IR825@PEI-PEG nano-complex which exhibits great dispersity in physiological solutions, excellent photostability, and is able to efficiently load chemotherapeutic drug doxorubicin (DOX) via a unique strategy different from drug loading in conventional amphiphilic polymer-based DDSs. In vivo animal experiments uncover that IR825@PEI-PEG/DOX upon intravenous injection into tumor-bearing mice shows rather high tumor uptake as illustrated by photoacoustic imaging. In vivo combined photothermal & chemotherapy is then carried out, demonstrating great synergistic anti-tumor therapeutic effect remarkably superior to those achieved by the respective mono-therapies. Hence, we present a novel type of nanoscale DDSs based on nano-assemblies of small molecules without involving amphiphilic polymers, promising for imaging-guided combination cancer therapy. |
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| Keywords: | J-aggregates Organic NIR dye Drug delivery systems Photothermal therapy Combination therapy |
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