Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system

Keun Sang Oh,1 Ji Young Yhee,2 Dong-Eun Lee,3 Kwangmeyung Kim,2 Ick Chan Kwon,2 Jae Hong Seo,4 Sang Yoon Kim,5 Soon Hong Yuk1,4 1College of Pharmacy, Korea University, Sejong, 2Biomedical Research Center, Korea Institute of Science and Technology, Seoul, 3Advanced Radiation Technology Institute, K...

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Autores principales: Oh KS, Yhee JY, Lee DE, Kim K, Kwon IC, Seo JH, Kim SY, Yuk SH
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Publicado: Dove Medical Press 2014
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spelling oai:doaj.org-article:c955c56f594e4638a55abf6982216a262021-12-02T03:58:30ZAccurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system1178-2013https://doaj.org/article/c955c56f594e4638a55abf6982216a262014-06-01T00:00:00Zhttp://www.dovepress.com/accurate-sequential-detection-of-primary-tumor-and-metastatic-lymphati-a17246https://doaj.org/toc/1178-2013 Keun Sang Oh,1 Ji Young Yhee,2 Dong-Eun Lee,3 Kwangmeyung Kim,2 Ick Chan Kwon,2 Jae Hong Seo,4 Sang Yoon Kim,5 Soon Hong Yuk1,4 1College of Pharmacy, Korea University, Sejong, 2Biomedical Research Center, Korea Institute of Science and Technology, Seoul, 3Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeonbuk, 4Biomedical Research Center, Korea University Guro Hospital, Seoul, 5Department of Otolaryngology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea Abstract: Primary tumor and tumor-associated metastatic lymphatics have emerged as new targets for anticancer therapy, given that these are difficult to treat using traditional chemotherapy. In this study, docetaxel-loaded Pluronic nanoparticles with Flamma™ (FPR-675, fluorescence molecular imaging dye; DTX/FPR-675 Pluronic NPs) were prepared using a temperature-induced phase transition for accurate detection of metastatic lymphatics. Significant accumulation was seen at the primary tumor and in metastatic lymph nodes within a short time. Particle size, maximum drug loading capacity, and drug encapsulation efficiency of the docetaxel-loaded Pluronic NPs were approximately 10.34±4.28 nm, 3.84 wt%, and 94±2.67 wt%, respectively. Lymphatic tracking after local and systemic delivery showed that DTX/FPR-675 Pluronic NPs were more potent in tumor-bearing mice than in normal mice, and excised mouse lymphatics showed stronger near-infrared fluorescence intensity on the tumor-bearing side than on the non-tumor-bearing side at 60 minutes post-injection. In vivo cytotoxicity and efficacy data for the NPs demonstrated that the systemically administered NPs caused little tissue damage and had minimal side effects in terms of slow renal excretion and prolonged circulation in tumor-bearing mice, and rapid renal excretion in non-tumor-bearing mice using an in vivo real-time near-infrared fluorescence imaging system. These results clearly indicate that docetaxel-loaded Pluronic NPs could provide a strategy to achieve effective cancer therapy by simultaneous delivery to primary tumors, tumor lymphatics, and tumor-associated metastatic lymphatics. Keywords: metastatic lymphatics, primary tumor targeting, lymphatic tracking, temperature-induced phase transition, Pluronic nanoparticlesOh KSYhee JYLee DEKim KKwon ICSeo JHKim SYYuk SHDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 2955-2965 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Oh KS
Yhee JY
Lee DE
Kim K
Kwon IC
Seo JH
Kim SY
Yuk SH
Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system
description Keun Sang Oh,1 Ji Young Yhee,2 Dong-Eun Lee,3 Kwangmeyung Kim,2 Ick Chan Kwon,2 Jae Hong Seo,4 Sang Yoon Kim,5 Soon Hong Yuk1,4 1College of Pharmacy, Korea University, Sejong, 2Biomedical Research Center, Korea Institute of Science and Technology, Seoul, 3Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeonbuk, 4Biomedical Research Center, Korea University Guro Hospital, Seoul, 5Department of Otolaryngology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea Abstract: Primary tumor and tumor-associated metastatic lymphatics have emerged as new targets for anticancer therapy, given that these are difficult to treat using traditional chemotherapy. In this study, docetaxel-loaded Pluronic nanoparticles with Flamma™ (FPR-675, fluorescence molecular imaging dye; DTX/FPR-675 Pluronic NPs) were prepared using a temperature-induced phase transition for accurate detection of metastatic lymphatics. Significant accumulation was seen at the primary tumor and in metastatic lymph nodes within a short time. Particle size, maximum drug loading capacity, and drug encapsulation efficiency of the docetaxel-loaded Pluronic NPs were approximately 10.34±4.28 nm, 3.84 wt%, and 94±2.67 wt%, respectively. Lymphatic tracking after local and systemic delivery showed that DTX/FPR-675 Pluronic NPs were more potent in tumor-bearing mice than in normal mice, and excised mouse lymphatics showed stronger near-infrared fluorescence intensity on the tumor-bearing side than on the non-tumor-bearing side at 60 minutes post-injection. In vivo cytotoxicity and efficacy data for the NPs demonstrated that the systemically administered NPs caused little tissue damage and had minimal side effects in terms of slow renal excretion and prolonged circulation in tumor-bearing mice, and rapid renal excretion in non-tumor-bearing mice using an in vivo real-time near-infrared fluorescence imaging system. These results clearly indicate that docetaxel-loaded Pluronic NPs could provide a strategy to achieve effective cancer therapy by simultaneous delivery to primary tumors, tumor lymphatics, and tumor-associated metastatic lymphatics. Keywords: metastatic lymphatics, primary tumor targeting, lymphatic tracking, temperature-induced phase transition, Pluronic nanoparticles
format article
author Oh KS
Yhee JY
Lee DE
Kim K
Kwon IC
Seo JH
Kim SY
Yuk SH
author_facet Oh KS
Yhee JY
Lee DE
Kim K
Kwon IC
Seo JH
Kim SY
Yuk SH
author_sort Oh KS
title Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system
title_short Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system
title_full Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system
title_fullStr Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system
title_full_unstemmed Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system
title_sort accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/c955c56f594e4638a55abf6982216a26
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