title: Photodynamic therapy of melanoma skin cancer using carbon dot - chlorin e6 - hyaluronate conjugate.
abstract: Despite wide application of photodynamic therapy (PDT) for the treatment of melanoma skin cancers, there are strong biomedical unmet needs for the effective generation of singlet oxygen after targeted delivery of photosensitizers. Here, we investigated a facile PDT of melanoma skin cancer using transdermal carbon dot - chlorine e6 - hyaluronate (Cdot-Ce6-HA) conjugates. The Cdot-Ce6-HA conjugate was synthesized by the coupling reaction of diaminohexane modified HA (DAH-HA) with the carboxylic group of Ce6. The singlet oxygen generation of Cdot-Ce6-HA conjugates in aqueous solution was more significant than that of free Ce6. The enhanced transdermal and intracellular delivery of Cdot-Ce6-HA conjugates to B16F10 melanoma cells in tumor model mice were corroborated by confocal microscopy and two-photon microscopy. The laser irradiation after topical treatment with Cdot-Ce6-HA conjugates resulted in complete suppression of melanoma skin cancers. The antitumor effect was confirmed by histological analysis with H&E staining and TUNEL assay for tumor apoptosis. Taken together, we could confirm the feasibility of Cdot-Ce6-HA conjugate for transdermal PDT of melanoma skin cancers.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report on a facile transdermal photodynamic therapy (PDT) of melanoma skin cancer using carbon dot - chlorine e6 - hyaluronate (Cdot-Ce6-HA) conjugates. We found that the singlet oxygen generation of Cdot-Ce6-HA conjugates in aqueous solution was more significant than that of free Ce6. Confocal microscopy and two-photon microscopy clearly confirmed the enhanced transdermal and intracellular delivery of Cdot-Ce6-HA conjugates to B16F10 melanoma cells in tumor model mice. Taken together, we could confirm the feasibility of Cdot-Ce6-HA conjugate for transdermal PDT of melanoma skin cancers.
authors: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 790-784, Republic of Korea.
authors: Songeun
authors: S
authors: Beack
authors: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 790-784, Republic of Korea.
authors: Won Ho
authors: WH
authors: Kong
authors: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 790-784, Republic of Korea.
authors: Ho Sang
authors: HS
authors: Jung
authors: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 790-784, Republic of Korea.
authors: In Hwan
authors: IH
authors: Do
authors: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 790-784, Republic of Korea.
authors: Seulgi
authors: S
authors: Han
authors: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 790-784, Republic of Korea.
authors: Hyemin
authors: H
authors: Kim
authors: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, 65 Landsdowne St., Cambridge, MA 02139, USA.
authors: Ki Su
authors: KS
authors: Kim
authors: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, 65 Landsdowne St., Cambridge, MA 02139, USA.
authors: Seok Hyun
authors: SH
authors: Yun
authors: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang 790-784, Republic of Korea. Electronic address: skhanb@postech.ac.kr.
authors: Sei Kwang
authors: SK
authors: Hahn
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002244:Carbon / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002735:Chlorophyllides; D004058:Diffusion; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry; D011166:Porphyrins / Q000008:administration & dosage* / Q000737:chemistry; D045663:Quantum Dots; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D002735:Chlorophyllides; D053769:Nanocapsules; D058726:Nanoconjugates; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin; D002244:Carbon
keywords: Carbon dot; Chlorin e6; Hyaluronate; Photodynamic therapy; Transdermal delivery