title: Hyaluronic acid conjugated superparamagnetic iron oxide nanoparticle for cancer diagnosis and hyperthermia therapy.
abstract: Recently, superparamagnetic iron oxide nanoparticles (SPIONs) have been prepared for magnetic resonance (MR) imaging and hyperthermia therapy. Here, we have developed hyaluronic acid (HA) coated SPIONs primarily for use in a hyperthermia application with an MR diagnostic feature with hydrodynamic size measurement of 176nm for HA-PEG10-SPIONs and 149nm for HA-SPIONs. HA-coated SPIONs (HA-SPIONs) were prepared to target CD44-expressed cancer where the carrier was conjugated to PEG for analyzing longer circulation in blood as well as for biocompatibility (HA-PEG10 SPIONs). Characterization was conducted with TEM (shape), DLS (size), ELS (surface charge), TGA (content of polymer) and MRI (T2-relaxation time). The heating ability of both the HA-SPIONs and HA-PEG10-SPIONs was studied by AMF and SAR calculation. Cellular level tests were conducted using SCC7 and NIH3T3 cell lines to confirm cell viability and cell specific uptake. HA-SPIONs and HA-PEG10-SPIONs were injected to xenograft mice bearing the SCC7 cell line for MRI cancer diagnosis. We found that HA-SPION-injected mice tumors showed nearly 40% MR T2 contrast compared to the 20% MR T2 contrast of the HA-PEG10-SPION group over a 3h time period. Finally, in vitro hyperthermia studies were conducted in the SCC7 cell line that showed less than 40% cell viability for both HA-SPIONs and HA-PEG10-SPIONs in AMF treated cells. In conclusion, HA-SPIONs were targeted specifically to the CD44, and the hyperthermia effect of HA-SPIONs and HA-PEG10-SPIONs was found to be significant for future studies.
authors.affiliation: Department of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea. Electronic address: regeth@gmail.com.
authors.forename: Reju George
authors.initials: RG
authors.lastname: Thomas
authors.affiliation: DKC corporation (BioActs), Incheon, Republic of Korea.
authors.forename: Myeong Ju
authors.initials: MJ
authors.lastname: Moon
authors.affiliation: Department of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Hyegyeong
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Arathyram Ramachandra Kurup
authors.initials: AR
authors.lastname: Sasikala
authors.affiliation: Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju 561-756, Republic of Korea; Division of Mechanical Design Engineering, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Cheol Sang
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-746, South Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Park
authors.affiliation: Department of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea. Electronic address: yjeong@jnu.ac.kr.
authors.forename: Yong Yeon
authors.initials: YY
authors.lastname: Jeong
mesh_terms: D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry* / Q000648:ultrastructure; D004705:Endocytosis; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006979:Hyperthermia, Induced; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D013194:Staining and Labeling; D013696:Temperature; D013997:Time Factors
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; D006820:Hyaluronic Acid; C065507:ferumoxides
keywords: Hyaluronic acid (HA); Hyperthermia; Magnetic resonance imaging (MRI); SPION