Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment
This paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA<sub>2</sub>-dPEG-DOX<sub>2</sub>). A unique feature is the use of monodisperse PEG (dPEG). The modular appr...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10347 |
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| author | Krisztina S. Nagy Krisztina Toth Eva Pallinger Angela Takacs Laszlo Kohidai Angela Jedlovszky-Hajdu Domokos Mathe Noemi Kovacs Daniel S. Veres Krisztian Szigeti Kristof Molnar Eniko Krisch Judit E. Puskas |
| author_facet | Krisztina S. Nagy Krisztina Toth Eva Pallinger Angela Takacs Laszlo Kohidai Angela Jedlovszky-Hajdu Domokos Mathe Noemi Kovacs Daniel S. Veres Krisztian Szigeti Kristof Molnar Eniko Krisch Judit E. Puskas |
| author_sort | Krisztina S. Nagy |
| collection | DOAJ |
| description | This paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA<sub>2</sub>-dPEG-DOX<sub>2</sub>). A unique feature is the use of monodisperse PEG (dPEG). The modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues. Flow cytometry analysis showed that at 10 µM concentration, both free DOX and FA<sub>2</sub>-dPEG-DOX<sub>2</sub> would be taken up by 99.9% of triple-negative breast cancer cells in 2 h. Intratumoral injection to mice seemed to delay tumor growth more than intravenous delivery. The mouse health status, food, water consumption, and behavior remained unchanged during the observation. |
| first_indexed | 2024-03-10T06:59:31Z |
| format | Article |
| id | doaj.art-0da34d7b068e4fa1ae2aca48c9c2ecfd |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:59:31Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0da34d7b068e4fa1ae2aca48c9c2ecfd2023-11-22T16:08:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191034710.3390/ijms221910347Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and TreatmentKrisztina S. Nagy0Krisztina Toth1Eva Pallinger2Angela Takacs3Laszlo Kohidai4Angela Jedlovszky-Hajdu5Domokos Mathe6Noemi Kovacs7Daniel S. Veres8Krisztian Szigeti9Kristof Molnar10Eniko Krisch11Judit E. Puskas12Laboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, HungaryLaboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, HungaryDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, HungaryDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, HungaryDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, HungaryLaboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, HungaryHungarian Center of Excellence for Molecular Medicine (HCEMM), In Vivo Imaging Advanced Core Facility, Semmelweis University Site, 1094 Budapest, HungaryDepartment of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, HungaryDepartment of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, HungaryDepartment of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, HungaryDepartment of Food, Agricultural and Biological Engineering, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, 222 FABE, 1680 Madison Avenue, Wooster, OH 44691, USADepartment of Food, Agricultural and Biological Engineering, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, 222 FABE, 1680 Madison Avenue, Wooster, OH 44691, USADepartment of Food, Agricultural and Biological Engineering, College of Food, Agricultural, and Environmental Sciences, The Ohio State University, 222 FABE, 1680 Madison Avenue, Wooster, OH 44691, USAThis paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA<sub>2</sub>-dPEG-DOX<sub>2</sub>). A unique feature is the use of monodisperse PEG (dPEG). The modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues. Flow cytometry analysis showed that at 10 µM concentration, both free DOX and FA<sub>2</sub>-dPEG-DOX<sub>2</sub> would be taken up by 99.9% of triple-negative breast cancer cells in 2 h. Intratumoral injection to mice seemed to delay tumor growth more than intravenous delivery. The mouse health status, food, water consumption, and behavior remained unchanged during the observation.https://www.mdpi.com/1422-0067/22/19/10347folate-targeted cancer diagnosispolymer conjugatesmultivalencychemo-enzymatic synthesisin vitro screeningin vivo screening |
| spellingShingle | Krisztina S. Nagy Krisztina Toth Eva Pallinger Angela Takacs Laszlo Kohidai Angela Jedlovszky-Hajdu Domokos Mathe Noemi Kovacs Daniel S. Veres Krisztian Szigeti Kristof Molnar Eniko Krisch Judit E. Puskas Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment International Journal of Molecular Sciences folate-targeted cancer diagnosis polymer conjugates multivalency chemo-enzymatic synthesis in vitro screening in vivo screening |
| title | Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment |
| title_full | Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment |
| title_fullStr | Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment |
| title_full_unstemmed | Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment |
| title_short | Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment |
| title_sort | folate targeted monodisperse peg based conjugates made by chemo enzymatic methods for cancer diagnosis and treatment |
| topic | folate-targeted cancer diagnosis polymer conjugates multivalency chemo-enzymatic synthesis in vitro screening in vivo screening |
| url | https://www.mdpi.com/1422-0067/22/19/10347 |
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