title: Hyaluronic acid derivative-coated nanohybrid liposomes for cancer imaging and drug delivery.
abstract: Nanohybrid liposomes coated with amphiphilic hyaluronic acid-ceramide (HACE) was fabricated for targeted delivery of anticancer drug and in vivo cancer imaging. Nanohybrid liposomes including doxorubicin (DOX) and Magnevist, a contrast agent for magnetic resonance (MR) imaging, with 120-130nm mean diameter and a narrow size distribution were developed. DOX release from the developed formulation was improved at acidic pH (pH5.5 and 6.8) versus physiological pH (pH7.4). Cytotoxicity induced by the blank plain liposome was reduced by coating the outer surface of the nanohybrid liposome with HACE. Cellular uptake of DOX from the nanohybrid liposome was enhanced by HA and CD44 receptor interaction, versus the plain liposome. In vivo contrast-enhancing effects revealed that the nanohybrid liposome can be used as a tumor targeting MR imaging probe for cancer diagnosis. In a pharmacokinetic study in rats, in vivo clearance of DOX was decreased in the order DOX solution, plain liposome (F2), and nanohybrid liposome (F3), indicating prolonged circulation of the drug in the blood stream and improved therapeutic efficacy of the nanohybrid liposome (F3). Based on these findings, the nanohybrid liposomal system may be a useful candidate for real-time cancer diagnosis and therapy.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ju-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Polymer Science and Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hong Yeol
authors.initials: HY
authors.lastname: Yoon
authors.affiliation: College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Yoon
authors.affiliation: Biogenics Inc., Daejeon 305-510, Republic of Korea.
authors.forename: Seung-Hak
authors.initials: SH
authors.lastname: Ko
authors.affiliation: Biogenics Inc., Daejeon 305-510, Republic of Korea; Skin & Tech Inc., Seongnam 461-713, Republic of Korea.
authors.forename: Jae-Seong
authors.initials: JS
authors.lastname: Shim
authors.affiliation: Division of Magnetic Resonance Research, Korea Basic Science Institute, Ochang 363-883, Republic of Korea.
authors.forename: Jee-Hyun
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Polymer Science and Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 6, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 6, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: ddkim@snu.ac.kr.
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D008081:Liposomes; D004317:Doxorubicin; D006820:Hyaluronic Acid; D019786:Gadolinium DTPA
keywords: Doxorubicin; Hyaluronic acid–ceramide; Hybrid nanostructure; Lipid; Magnetic resonance imaging