Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells
The aim of this study is to fabricate nanophotosensitizers composed of methoxy poly(ethylene glycol) (mPEG), chlorin e6 (Ce6), and phenylboronic acid pinacol ester (PBAP) with diselenide linkages for reactive oxygen species (ROS)-sensitive photodynamic therapy (PDT) of cervical cancer cells. To fabr...
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| author | Ju-Il Yang Hye-Lim Lee Seon-Hee Choi Jungsoo Kim Young-Bob Yu Young-IL Jeong Dae-Hwan Kang |
| author_facet | Ju-Il Yang Hye-Lim Lee Seon-Hee Choi Jungsoo Kim Young-Bob Yu Young-IL Jeong Dae-Hwan Kang |
| author_sort | Ju-Il Yang |
| collection | DOAJ |
| description | The aim of this study is to fabricate nanophotosensitizers composed of methoxy poly(ethylene glycol) (mPEG), chlorin e6 (Ce6), and phenylboronic acid pinacol ester (PBAP) with diselenide linkages for reactive oxygen species (ROS)-sensitive photodynamic therapy (PDT) of cervical cancer cells. To fabricate nanophotosensitizers, Ce6 was conjugated with mPEG via selenocystamine linkage and then remaining carboxylic acid groups of Ce6 was attached to PBAP (mPEGseseCe6PBAP conjugates). Nanophotosensitizers of mPEGseseCe6PBAP conjugates were prepared by dialysis method. In transmission electron microscope (TEM) observation, nanophotosensitizers of mPEGseseCe6PBAP conjugates have spherical shapes and their diameters were less than 150 nm. The average diameter of mPEGseseCe6PBAP nanophotosensitizers was 92.7 ± 9.6 nm in particle size analysis. When H<sub>2</sub>O<sub>2</sub> was added to the nanophotosensitizer solution, nanophotosensitizers were sensitively disintegrated according to the H<sub>2</sub>O<sub>2</sub> concentration and then changed from monomodal distribution to multimodal distribution in particle size distribution. Furthermore, Ce6 release from nanophotosensitizers also increased according to the H<sub>2</sub>O<sub>2</sub> concentration. When H<sub>2</sub>O<sub>2</sub> was added to cell culture of HeLa human cervical cancer cells, intracellular Ce6 uptake of nanophotosensitizers were gradually increased according to the H<sub>2</sub>O<sub>2</sub> concentration, indicating that nanophotosensitizers showed ROS-sensitive delivery of Ce6 against cancer cells.As well as free Ce6, nanophotosensitizers in the absence of light irradiation have low intrinsic cytotoxicity against RAW264.7 cells and HeLa cells. However, nanophotosensitizers induced cell death dose-dependently under light irradiation. Especially, nanophotosensitizers showed significantly higher ROS generation and phototoxicity against HeLa cells in vitro. When nanophotosensitizers were intravenously administered to animal tumor xenograft model of HeLa cells, tumor tissues revealed stronger fluorescence intensity than other tissues by light irradiation while absence of light irradiation induced relatively lower fluorescence intensity in tumor tissues, indicating that nanophotosensitizers have sensitivity against oxidative stress in tumor tissues. We suggest that nanophotosensitizers of mPEGseseCe6PBAP conjugates are promising vehicle for PDT of cervical cancer cells. |
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| language | English |
| last_indexed | 2024-03-10T03:34:51Z |
| publishDate | 2021-12-01 |
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| spelling | doaj.art-8a72ceb47ddd48e9adb002ec1c8970742023-11-23T11:48:41ZengMDPI AGMaterials1996-19442021-12-0115113810.3390/ma15010138Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer CellsJu-Il Yang0Hye-Lim Lee1Seon-Hee Choi2Jungsoo Kim3Young-Bob Yu4Young-IL Jeong5Dae-Hwan Kang6Department of Medical Science, Pusan National University School of Medicine, Yangsan 50612, KoreaResearch Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaResearch Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaResearch Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaDepartment of Emergency Medical Rescue, Nambu University, Gwangju 62271, KoreaResearch Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaDepartment of Medical Science, Pusan National University School of Medicine, Yangsan 50612, KoreaThe aim of this study is to fabricate nanophotosensitizers composed of methoxy poly(ethylene glycol) (mPEG), chlorin e6 (Ce6), and phenylboronic acid pinacol ester (PBAP) with diselenide linkages for reactive oxygen species (ROS)-sensitive photodynamic therapy (PDT) of cervical cancer cells. To fabricate nanophotosensitizers, Ce6 was conjugated with mPEG via selenocystamine linkage and then remaining carboxylic acid groups of Ce6 was attached to PBAP (mPEGseseCe6PBAP conjugates). Nanophotosensitizers of mPEGseseCe6PBAP conjugates were prepared by dialysis method. In transmission electron microscope (TEM) observation, nanophotosensitizers of mPEGseseCe6PBAP conjugates have spherical shapes and their diameters were less than 150 nm. The average diameter of mPEGseseCe6PBAP nanophotosensitizers was 92.7 ± 9.6 nm in particle size analysis. When H<sub>2</sub>O<sub>2</sub> was added to the nanophotosensitizer solution, nanophotosensitizers were sensitively disintegrated according to the H<sub>2</sub>O<sub>2</sub> concentration and then changed from monomodal distribution to multimodal distribution in particle size distribution. Furthermore, Ce6 release from nanophotosensitizers also increased according to the H<sub>2</sub>O<sub>2</sub> concentration. When H<sub>2</sub>O<sub>2</sub> was added to cell culture of HeLa human cervical cancer cells, intracellular Ce6 uptake of nanophotosensitizers were gradually increased according to the H<sub>2</sub>O<sub>2</sub> concentration, indicating that nanophotosensitizers showed ROS-sensitive delivery of Ce6 against cancer cells.As well as free Ce6, nanophotosensitizers in the absence of light irradiation have low intrinsic cytotoxicity against RAW264.7 cells and HeLa cells. However, nanophotosensitizers induced cell death dose-dependently under light irradiation. Especially, nanophotosensitizers showed significantly higher ROS generation and phototoxicity against HeLa cells in vitro. When nanophotosensitizers were intravenously administered to animal tumor xenograft model of HeLa cells, tumor tissues revealed stronger fluorescence intensity than other tissues by light irradiation while absence of light irradiation induced relatively lower fluorescence intensity in tumor tissues, indicating that nanophotosensitizers have sensitivity against oxidative stress in tumor tissues. We suggest that nanophotosensitizers of mPEGseseCe6PBAP conjugates are promising vehicle for PDT of cervical cancer cells.https://www.mdpi.com/1996-1944/15/1/138nanophotosensitizerROS-sensitivephotodynamic therapycervical cancerchlorin e6 |
| spellingShingle | Ju-Il Yang Hye-Lim Lee Seon-Hee Choi Jungsoo Kim Young-Bob Yu Young-IL Jeong Dae-Hwan Kang Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells Materials nanophotosensitizer ROS-sensitive photodynamic therapy cervical cancer chlorin e6 |
| title | Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells |
| title_full | Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells |
| title_fullStr | Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells |
| title_full_unstemmed | Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells |
| title_short | Reactive Oxygen Species-Sensitive Nanophotosensitizers of Methoxy Poly(ethylene glycol)-Chlorin e6/Phenyl Boronic Acid Pinacol Ester Conjugates Having Diselenide Linkages for Photodynamic Therapy of Cervical Cancer Cells |
| title_sort | reactive oxygen species sensitive nanophotosensitizers of methoxy poly ethylene glycol chlorin e6 phenyl boronic acid pinacol ester conjugates having diselenide linkages for photodynamic therapy of cervical cancer cells |
| topic | nanophotosensitizer ROS-sensitive photodynamic therapy cervical cancer chlorin e6 |
| url | https://www.mdpi.com/1996-1944/15/1/138 |
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