title: Graphene oxide-incorporated pH-responsive folate-albumin-photosensitizer nanocomplex as image-guided dual therapeutics.
abstract: The objective of this study was to develop an active-targeted, pH-responsive albumin-photosensitizer-incorporated graphene oxide nanocomplex as an image-guided theranostic agent for dual therapies. Herein, bovine serum albumin (BSA)-cis-aconityl pheophorbide-a (c-PheoA) conjugate was complexed with graphene oxide (GO) at ratios of 1:1, 1:0.5, and 1:0.1 with the mean hydrodynamic diameter of the resulting complex being 100-200nm. Further, with the 1:0.5 ratio, we developed a folate-BSA-c-PheoA conjugate:GO complex incorporated free PheoA (PheoA+GO:FA-BSA-c-PheoA NC) with a mean hydrodynamic diameter of 182.0±33.2nm. The release study showed that the photosensitizer from the nanocomplex was released rapidly at pH5.5 compared to that at pH7.4 when incubated for 24h. Cellular uptake results showed that the PheoA+GO:FA-BSA-c-PheoA NCs was readily taken up by B16F10 and MCF7 cancer cells. In vitro phototoxicity results showed that PheoA+GO:FA-BSA-c-PheoA NC has a higher efficacy against cancer cells than free PheoA, thereby demonstrating the synergistic effect of PS and GO in response to a single laser of 670nm. In vivo and ex vivo bioimaging results showed that fluorescence signals of higher intensity were observed in the tumor area of mice treated with PheoA+GO:FA-BSA-c-PheoA NC than those in the tumor of mice treated with free PheoA, thereby suggesting that the targeted nanocomplex selectively accumulated in the tumor area compared to free PheoA. Through antitumor study, PheoA+GO:FA-BSA-c-PheoA NC showed a synergistic effect in tumor-bearing mice by a single 671nm laser treatment. These results demonstrate that our prepared PheoA+GO:FA-BSA-c-PheoA NC can be used as a theranostic agent in phototherapies and for the photodiagnosis of cancer.
authors.affiliation: College of Pharmacy, Gachon University, Incheon 406-799, South Korea.
authors.forename: Gantumur
authors.initials: G
authors.lastname: Battogtokh
authors.affiliation: College of Pharmacy, Gachon University, Incheon 406-799, South Korea. Electronic address: youngtakko@gachon.ac.kr.
authors.forename: Young Tag
authors.initials: YT
authors.lastname: Ko
mesh_terms: D000156:Aconitic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D065546:Drug Liberation; D005492:Folic Acid / Q000737:chemistry*; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D007834:Lasers; D061986:MCF-7 Cells; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D058726:Nanoconjugates / Q000737:chemistry*; D010087:Oxides; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D058726:Nanoconjugates; D010087:Oxides; D017319:Photosensitizing Agents; D002734:Chlorophyll; D012710:Serum Albumin, Bovine; C064873:aconitic anhydride; D006108:Graphite; D000156:Aconitic Acid; D005492:Folic Acid; C032623:pheophorbide a
keywords: Albumin; Graphene oxide; Nanocomplex; Photosensitizer; Phototherapy; pH-Responsive linkage