Journal
ACTA BIOMATERIALIA
Volume 26, Issue -, Pages 295-305Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2015.08.027
Keywords
Carbon dot; Chlorin e6; Hyaluronate; Transdermal delivery; Photodynamic therapy
Funding
- NRF - MEST [2012R1A2A2A06045773]
- Korean Health Technology R&D Project, Ministry of Health and Welfare, Korea [HI14C1658]
- MSIP (Ministry of Science, ICT and Future Planning), Korea [NIPA-2014-H0201-14-1001]
- Pohang Center for Evaluation of Biomaterials (Pohang Technopark)
- Korea Health Promotion Institute [HI14C1658020015] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Ministry of Public Safety & Security (MPSS), Republic of Korea [R0346-15-1007] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2012R1A2A2A06045773, 2015H1A2A1034059] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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. Statement of Significance 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. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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