Hyaluronic Acid-Conjugated with Hyperbranched Chlorin e6 Using Disulfide Linkage and Its Nanophotosensitizer for Enhanced Photodynamic Therapy of Cancer Cells
| Autor: | Byung-Hoon Kim, Seunggon Jung, Young-Il Jeong, Chang-Min Lee, Hanjin Kwon, Shin Jung, Sa-Hoe Lim, Yong Ho Shim, Do Hoon Kim, Doo Man Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Disulfide Linkage
medicine.medical_treatment branched polymer Photodynamic therapy 02 engineering and technology Conjugated system lcsh:Technology Dithiothreitol Article CD44-receptor 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tetramer Cystamine Hyaluronic acid medicine General Materials Science Photosensitizer lcsh:Microscopy lcsh:QC120-168.85 lcsh:QH201-278.5 lcsh:T 021001 nanoscience & nanotechnology chemistry photodynamic therapy lcsh:TA1-2040 030220 oncology & carcinogenesis Biophysics lcsh:Descriptive and experimental mechanics lcsh:Electrical engineering. Electronics. Nuclear engineering lcsh:Engineering (General). Civil engineering (General) 0210 nano-technology lcsh:TK1-9971 Chlorin e6 redox sensitive |
| Zdroj: | Materials Volume 12 Issue 19 Materials, Vol 12, Iss 19, p 3080 (2019) |
| ISSN: | 1996-1944 |
| Popis: | The main purpose of this study is to synthesize novel types of nanophotosensitizers that are based on hyperbranched chlorin e6 (Ce6) via disulfide linkages. Moreover, hyperbranched Ce6 was conjugated with hyaluronic acid (HA) for CD44-receptor mediated delivery and redox-sensitive photodynamic therapy (PDT) against cancer cells. Hyperbranched Ce6 was considered to make novel types of macromolecular photosensitizer since most of the previous studies regarding nanophotosensizers are concerned with simple conjugation between monomeric units of photosensitizer and polymer materials. Hyperbranched Ce6 was synthesized by conjugation of Ce6 each other while using disulfide linkage. To synthesize Ce6 tetramer, carboxyl groups of Ce6 were conjugated with cystamine and three equivalents of Ce6 were then conjugated again with the end of amine groups of Ce6-cystamine. To synthesize Ce6 decamer as a hyperbranched Ce6, six equivalents of Ce6 was conjugated with the end of Ce6 tetramer via cystamine linkage. Furthermore, HA-cystamine was attached with Ce6 tetramer or Ce6 decamer to synthesize HA-Ce6 tetramer (Ce6tetraHA) or HA-Ce6 decamer (Ce6decaHA) conjugates. Ce6tetraHA and Ce6decaHA nanophotosensitizers showed small diameters of less than 200 nm. The addition of dithiothreitol (DTT) and hyaluronidase (HAse) induced a faster Ce6 release rate in vitro drug release study, which indicated that Ce6tetraHA nanophotosensitizers possess redox-sensitive and HAse-sensitive release properties. Ce6tetraHA nanophotosensitizers showed higher intracellular Ce6 accumulation, higher ROS generation, and higher PDT efficacy than that of Ce6 alone. Ce6tetraHA nanophotosensitizers responded to the CD44 receptor of cancer cell surface, i.e., the pre-treatment of HA blocked CD44 receptor of U87MG or HCT116 cells and then inhibited delivery of nanophotosensitizers in vitro cell culture study. Furthermore, in vivo tumorxenograft study showed that fluorescence intensity in the tumor tissues was stronger than those of other organs, while CD44 receptor blocking by HA pretreatment induced a decrease of fluorescence intensity in tumor tissues when compared to liver. These results indicated that Ce6tetraHA nanophotosensitizers delivered to tumors by redox-sensitive and CD44-sensitive manner. |
| Databáze: | OpenAIRE |
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