title: Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system.
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.
authors: College of Pharmacy, Korea University, Sejong, Seoul, Republic of Korea.
authors: Keun Sang
authors: KS
authors: Oh
authors: Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Seoul, Republic of Korea.
authors: Ji Young
authors: JY
authors: Yhee
authors: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeonbuk, Seoul, Republic of Korea.
authors: Dong-Eun
authors: DE
authors: Lee
authors: Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Seoul, Republic of Korea.
authors: Kwangmeyung
authors: K
authors: Kim
authors: Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Seoul, Republic of Korea.
authors: Ick Chan
authors: IC
authors: Kwon
authors: Biomedical Research Center, Korea University Guro Hospital, Seoul, Seoul, Republic of Korea.
authors: Jae Hong
authors: JH
authors: Seo
authors: Department of Otolaryngology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea.
authors: Sang Yoon
authors: SY
authors: Kim
authors: College of Pharmacy, Korea University, Sejong, Seoul, Republic of Korea ; Biomedical Research Center, Korea University Guro Hospital, Seoul, Seoul, Republic of Korea.
authors: Soon Hong
authors: SH
authors: Yuk
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002417:Cattle; D000077143:Docetaxel; D006361:Heating / Q000379:methods*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058726:Nanoconjugates / Q000737:chemistry / Q000627:therapeutic use; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology* / Q000556:secondary*; D044367:Phase Transition; D020442:Poloxamer / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D058726:Nanoconjugates; D043823:Taxoids; D020442:Poloxamer; D000077143:Docetaxel
keywords: Pluronic nanoparticles; lymphatic tracking; metastatic lymphatics; primary tumor targeting; temperature-induced phase transition