title: Effect of HIFU treatment on tumor targeting efficacy of docetaxel-loaded Pluronic nanoparticles.
abstract: Numerous studies have been performed to identify the microenvironment of solid tumors, which is responsible for the insufficient delivery of anticancer drugs to tumor cells due to the poorly organized vasculature and the increased interstitial fluid pressure. As a result, the extravasation of convection-dependent agents including NPs is severely limited. Therefore, we have demonstrated the feasibility of targeting an enhancement of docetaxel-loaded Pluronic nanoparticles (NPs) using high-intensity focused ultrasound (HIFU) as an external stimulus-induced clinical system in tumor tissue. The efficient extravasation of NPs into the interior cells in tumor tissue was induced by relatively low HIFU exposure without apparent acute tissue damage. The enhanced targeting of NPs with near-infrared fluorescence dye was observed in tumor-bearing mice with various HIFU exposures. As a result, the greatest accumulation of NPs at the tumor tissue was observed at an HIFU exposure of 20 W/cm(2). However, the tumor tissue above at 20 W/cm(2) appeared to be destroyed and the tumor targetability of NPs was significantly decreased owing to thermal ablation with necrosis, resulting in the destruction of the tumor tissue and the blood vessels. In particular, a cross-sectional view of the tumor tissue verified that the NPs migrated into the middle of the tumor tissue upon HIFU exposure. The preliminary results here demonstrate that HIFU exposure through non-thermal mechanisms can aid with the extravasation of NPs into the interior cells of tumors and increase the therapeutic effect in enhanced and targeted cancer therapy.
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejongro, Sejong 339-700, Republic of Korea.
authors.forename: Keun Sang
authors.initials: KS
authors.lastname: Oh
authors.affiliation: Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom Ro, Mapo-gu, Seoul 121-742, Republic of Korea; Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Sungbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Hyounkoo
authors.initials: H
authors.lastname: Han
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejongro, Sejong 339-700, Republic of Korea.
authors.forename: Byeong Deok
authors.initials: BD
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejongro, Sejong 339-700, Republic of Korea.
authors.forename: Minae
authors.initials: M
authors.lastname: Lee
authors.affiliation: Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom Ro, Mapo-gu, Seoul 121-742, Republic of Korea.
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Republic of Korea.
authors.forename: Dong Wan
authors.initials: DW
authors.lastname: Seo
authors.affiliation: Biomedical Research Center, Korea University Guro Hospital, 148-1 Gurodong-ro, Guro-gu, Seoul 152-703, Republic of Korea.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Seo
authors.affiliation: Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Sungbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Sungbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejongro, Sejong 339-700, Republic of Korea; Biomedical Research Center, Korea University Guro Hospital, 148-1 Gurodong-ro, Guro-gu, Seoul 152-703, Republic of Korea. Electronic address: shyuk@korea.ac.kr.
authors.forename: Soon Hong
authors.initials: SH
authors.lastname: Yuk
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods*; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D020442:Poloxamer / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry; D013024:Soybean Oil / Q000737:chemistry; D043823:Taxoids / Q000494:pharmacology*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D011136:Polysorbates; D043823:Taxoids; D020442:Poloxamer; D000077143:Docetaxel; D013024:Soybean Oil
keywords: Effective cancer therapy; Extravasation; Pluronic nanoparticles; Targeting enhancement; Ultrasound-induced