title: Image-guided synergistic photothermal therapy using photoresponsive imaging agent-loaded graphene-based nanosheets.
abstract: We report the image-guided synergistic photothermal antitumor effects of photoresponsive near-infrared (NIR) imaging agent, indocyanine green (ICG), by loading onto hyaluronic acid-anchored, reduced graphene oxide (HArGO) nanosheets. Loading of ICG onto either rGO (ICG/rGO) or HArGO (ICG/HArGO) substantially improved the photostability of photoresponsive ICG upon NIR irradiation. After 1min of irradiation, the NIR absorption peak of ICG almost disappeared whereas the peak of ICG on rGO or HArGO was retained even after 5min of irradiation. Compared with plain rGO, HArGO provided greater cellular delivery of ICG and photothermal tumor cell-killing effects upon laser irradiation in CD44-positive KB cells. The temperature of cell suspensions treated with ICG/HArGO was 2.4-fold higher than that of cells treated with free ICG. Molecular imaging revealed that intravenously administered ICG/HArGO accumulated in KB tumor tissues higher than ICG/rGO or free ICG. Local temperatures in tumor tissues of laser-irradiated KB cell-bearing nude mice were highest in those intravenously administered ICG/HArGO, and were sufficient to trigger thermal-induced complete tumor ablation. Immunohistologically stained tumors also showed the highest percentages of apoptotic cells in the group treated with ICG/HArGO. These results suggest that photoresponsive ICG-loaded HArGO nanosheets could serve as a potential theranostic nano-platform for image-guided and synergistic photothermal antitumor therapy.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Miao
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Gayong
authors.initials: G
authors.lastname: Shim
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of Korea.
authors.forename: Gunwoo
authors.initials: G
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Soondong
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Bio-industrial Technologies, Konkuk University, Seoul, Republic of Korea.
authors.forename: Young Bong
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of Korea.
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea. Electronic address: ohyk@snu.ac.kr.
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006108:Graphite / Q000008:administration & dosage* / Q000032:analysis; D006801:Humans; D007208:Indocyanine Green / Q000008:administration & dosage* / Q000032:analysis; D007275:Injections, Intravenous; D007624:KB Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049329:Nanostructures / Q000008:administration & dosage* / Q000032:analysis; D010789:Phototherapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D006108:Graphite; D007208:Indocyanine Green
keywords: Image-guided photothermal therapy; Indocyanine green; Photoresponsive imaging agent; Reduced graphene oxide nanosheets; Theranostics