title: Safety and tumor tissue accumulation of pegylated graphene oxide nanosheets for co-delivery of anticancer drug and photosensitizer.
abstract: Here, we report the safety, tumor accumulation and potential of polyethylene glycol-grafted graphene oxide (pGO) as a multimodal nanocarrier of photosensitizers and synergistic anticancer agents. First, both graphene oxide (GO) and pGO were synthesized, and their in vitro and in vivo toxicities were tested. When 80 mg/kg was injected intravenously into mice, there was 100% fatality in the GO-treated group, but 100% survival among mice treated with pGO nanosheets. Treatment of cells with a photosensitizer chlorin e6 (Ce6) in pGO nanophysisorplexes significantly enhanced cellular delivery compared to that seen with Ce6 alone. The combination and dose reduction indexes revealed that combining doxorubicin (Dox) with Ce6 with at a molar ratio of 1:2 provided the highest synergism. The Ce6- and Dox-loaded pGO nanophysisorplexes (Ce6/Dox/pGO) were 148.0 ± 18.0 nm in size. Molecular imaging of mice showed that Ce6/Dox/pGO could accumulate in tumor tissues over 3 days. Moreover, in SCC tumor-bearing mice, the photodynamic anticancer effects of Ce6/Dox/pGO were higher than those of Ce6/pGO or Dox/pGO. Moreover, tumor sections from illuminated mice treated with Ce6/Dox/pGO showed substantial disruption of tumor nuclei, whereas the other groups did not. Our results suggest that pGO nanosheets have superior in vivo safety relative to GO, and that it is possible to enhance the tumor tissue distribution and photodynamic anticancer effects of systemically administered Ce6 by forming multimodal nanophysisorplexes with pGO and synergistic anticancer chemotherapeutics such as Dox.
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Wenjun
authors: W
authors: Miao
authors: Gayong
authors: G
authors: Shim
authors: Sangbin
authors: S
authors: Lee
authors: Soondong
authors: S
authors: Lee
authors: Yearn Seong
authors: YS
authors: Choe
authors: Yu-Kyoung
authors: YK
authors: Oh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D004357:Drug Synergism; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D006108:Graphite / Q000009:adverse effects*; D051379:Mice; D053758:Nanoparticles / Q000009:adverse effects* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000009:adverse effects*; D011166:Porphyrins / Q000494:pharmacology; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; D011092:Polyethylene Glycols; C062985:phytochlorin; D006108:Graphite; D004317:Doxorubicin