Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak
This paper describes the synthesis and characterization of new bivalent folate-targeted PEGylated doxorubicin (FA2-dPEG-DOX2) made by modular chemo-enzymatic processes using Candida antarctica lipase B (CALB) as a biocatalyst. Unique features are the use of monodisperse PEG (dPEG) and the synthesis...
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ftmdpi:oai:mdpi.com:/2073-4360/14/14/2900/ 2023-08-20T04:01:54+02:00 Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak Judit E. Puskas Gayatri Shrikhande Eniko Krisch Kristof Molnar 2022-07-16 application/pdf https://doi.org/10.3390/polym14142900 EN eng Multidisciplinary Digital Publishing Institute Polymer Applications https://dx.doi.org/10.3390/polym14142900 https://creativecommons.org/licenses/by/4.0/ Polymers; Volume 14; Issue 14; Pages: 2900 enzyme catalysis discrete poly(ethylene glycol) dPEG polymer drug conjugate modular assembly doxorubicin folic acid Michael addition Text 2022 ftmdpi https://doi.org/10.3390/polym14142900 2023-08-01T05:44:07Z This paper describes the synthesis and characterization of new bivalent folate-targeted PEGylated doxorubicin (FA2-dPEG-DOX2) made by modular chemo-enzymatic processes using Candida antarctica lipase B (CALB) as a biocatalyst. Unique features are the use of monodisperse PEG (dPEG) and the synthesis of thiol-functionalized folic acid yielding exclusive γ-conjugation of folic acid (FA) to dPEG. The polymer-based drug conjugate is built up by a series of transesterification and Michael addition reactions all catalyzed be CALB. In comparison with other methods in the literature, the modular approach with enzyme catalysis leads to selectivity, full conversion and high yield, and no transition metal catalyst residues. The intermediate product with four acrylate groups is an excellent platform for Michael-addition-type reactions for a wide variety of biologically active molecules. The chemical structures were confirmed by nuclear magnetic resonance spectroscopy (NMR). Flow cytometry analysis showed that, at 10 µM concentration, both free DOX and FA2-dPEG-DOX2 were taken up by 99.9% of triple-negative breast cancer cells in 2 h. Fluorescence was detected for 5 days after injecting compound IV into mice. Preliminary results showed that intra-tumoral injection seemed to delay tumor growth more than intravenous delivery. Text Antarc* Antarctica MDPI Open Access Publishing Polymers 14 14 2900 |
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MDPI Open Access Publishing |
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English |
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enzyme catalysis discrete poly(ethylene glycol) dPEG polymer drug conjugate modular assembly doxorubicin folic acid Michael addition |
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enzyme catalysis discrete poly(ethylene glycol) dPEG polymer drug conjugate modular assembly doxorubicin folic acid Michael addition Judit E. Puskas Gayatri Shrikhande Eniko Krisch Kristof Molnar Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak |
topic_facet |
enzyme catalysis discrete poly(ethylene glycol) dPEG polymer drug conjugate modular assembly doxorubicin folic acid Michael addition |
description |
This paper describes the synthesis and characterization of new bivalent folate-targeted PEGylated doxorubicin (FA2-dPEG-DOX2) made by modular chemo-enzymatic processes using Candida antarctica lipase B (CALB) as a biocatalyst. Unique features are the use of monodisperse PEG (dPEG) and the synthesis of thiol-functionalized folic acid yielding exclusive γ-conjugation of folic acid (FA) to dPEG. The polymer-based drug conjugate is built up by a series of transesterification and Michael addition reactions all catalyzed be CALB. In comparison with other methods in the literature, the modular approach with enzyme catalysis leads to selectivity, full conversion and high yield, and no transition metal catalyst residues. The intermediate product with four acrylate groups is an excellent platform for Michael-addition-type reactions for a wide variety of biologically active molecules. The chemical structures were confirmed by nuclear magnetic resonance spectroscopy (NMR). Flow cytometry analysis showed that, at 10 µM concentration, both free DOX and FA2-dPEG-DOX2 were taken up by 99.9% of triple-negative breast cancer cells in 2 h. Fluorescence was detected for 5 days after injecting compound IV into mice. Preliminary results showed that intra-tumoral injection seemed to delay tumor growth more than intravenous delivery. |
format |
Text |
author |
Judit E. Puskas Gayatri Shrikhande Eniko Krisch Kristof Molnar |
author_facet |
Judit E. Puskas Gayatri Shrikhande Eniko Krisch Kristof Molnar |
author_sort |
Judit E. Puskas |
title |
Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak |
title_short |
Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak |
title_full |
Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak |
title_fullStr |
Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak |
title_full_unstemmed |
Multifunctional PEG Carrier by Chemoenzymatic Synthesis for Drug Delivery Systems: In Memory of Professor Andrzej Dworak |
title_sort |
multifunctional peg carrier by chemoenzymatic synthesis for drug delivery systems: in memory of professor andrzej dworak |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2022 |
url |
https://doi.org/10.3390/polym14142900 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Polymers; Volume 14; Issue 14; Pages: 2900 |
op_relation |
Polymer Applications https://dx.doi.org/10.3390/polym14142900 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/polym14142900 |
container_title |
Polymers |
container_volume |
14 |
container_issue |
14 |
container_start_page |
2900 |
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1774712277640937472 |