title: Iodinated hyaluronic acid oligomer-based nanoassemblies for tumor-targeted drug delivery and cancer imaging.
abstract: Nano-sized self-assemblies based on amphiphilic iodinated hyaluronic acid (HA) were developed for use in cancer diagnosis and therapy. 2,3,5-Triiodobenzoic acid (TIBA) was conjugated to an HA oligomer as a computed tomography (CT) imaging modality and a hydrophobic residue. Nanoassembly based on HA-TIBA was fabricated for tumor-targeted delivery of doxorubicin (DOX). Cellular uptake of DOX from nanoassembly, compared to a DOX solution group, was enhanced via an HA-CD44 receptor interaction, and subsequently, the in vitro antitumor efficacy of DOX-loaded nanoassembly was improved in SCC7 (CD44 receptor positive squamous cell carcinoma) cells. Cy5.5, a near-infrared fluorescence (NIRF) dye, was attached to the HA-TIBA conjugate and the in vivo tumor targetability of HA-TIBA nanoassembly, which is based on the interaction between HA and CD44 receptor, was demonstrated in a NIRF imaging study using an SCC7 tumor-xenografted mouse model. Tumor targeting and cancer diagnosis with HA-TIBA nanoassembly were verified in a CT imaging study using the SCC7 tumor-xenografted mouse model. In addition to efficient cancer diagnosis using NIRF and CT imaging modalities, improved antitumor efficacies were shown. HA and TIBA can be used to produce HA-TIBA nanoassembly that may be a promising theranostic nanosystem for cancers that express the CD44 receptor.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea. Electronic address: hjcho@kangwon.ac.kr.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
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; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D006820:Hyaluronic Acid / Q000737:chemistry*; D007275:Injections, Intravenous; D007455:Iodine / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D019265:Spectroscopy, Near-Infrared; D015898:Tomography Scanners, X-Ray Computed; D014283:Triiodobenzoic Acids / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014283:Triiodobenzoic Acids; D004317:Doxorubicin; D006820:Hyaluronic Acid; D007455:Iodine
keywords: Hyaluronic acid; In vivo imaging; Nanoassemblies; Triiodobenzoic acid; Tumor-targeted therapy