한빛사 논문
Abstract
Kyung Hyun Min†‡, Hyun Su Min†, Hong Jae Lee§, Dong Jin Park∥, Ji Young Yhee†, Kwangmeyung Kim†, Ick Chan Kwon*†, Seo Young Jeong∥, Oscar F. Silvestre‡, Xiaoyuan Chen‡, Yu-Shik Hwang§, Eun-Cheol Kim⊥, and Sang Cheon Lee*§
† Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea
‡ Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892, United States
§ Department of Maxillofacial Biomedical Engineering & Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 130-701, Republic of Korea
∥ Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea
⊥ Department of Maxillofacial Tissue Regeneration and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul 130-701, Republic of Korea
*Address correspondence to Sang Cheon Lee
Abstract
We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO3) hybrid nanoparticles (DOX-CaCO3-MNPs) through a block copolymer templated in situ mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO2) bubbles and showed excellent echo persistence. In vivo results demonstrated that the DOX-CaCO3-MNPs generated CO2 bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO3-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO2 bubbles necessary for US contrast. The DOX-CaCO3-MNPs could also trigger the DOX release simultaneously with CO2 bubble generation at the acidic tumoral environment. The DOX-CaCO3-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers.
Keywords: theranostics; carbon dioxide; mineralization; nanobubble; ultrasound; drug delivery
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