Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer Therapy
Using an endogenous carrier is the best method to address the biocompatibility of carriers in the drug delivery field. Herein, we prepared a glutathione-responsive paclitaxel prodrug micelle based on an endogenous molecule of L-glutathione oxidized (GSSG) for cancer therapy using one-pot synthesis....
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-09-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/16/9/1178 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850259848305836032 |
|---|---|
| author | Xiao Duan Qiang Wang Yue Wang Xinping Liu Manman Lu Zhifang Li Xuelian Jiang Jingquan Ji |
| author_facet | Xiao Duan Qiang Wang Yue Wang Xinping Liu Manman Lu Zhifang Li Xuelian Jiang Jingquan Ji |
| author_sort | Xiao Duan |
| collection | DOAJ |
| description | Using an endogenous carrier is the best method to address the biocompatibility of carriers in the drug delivery field. Herein, we prepared a glutathione-responsive paclitaxel prodrug micelle based on an endogenous molecule of L-glutathione oxidized (GSSG) for cancer therapy using one-pot synthesis. The carboxyl groups in L-glutathione oxidized were reacted with the hydroxyl group in paclitaxel (PTX) using the catalysts dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Then, the amino-polyethylene glycol monomethyl ether (mPEG-NH<sub>2</sub>) was conjugated with GSSG to prepare PTX-GSSG-PEG. The structure of PTX-GSSG-PEG was characterized using infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS). The drug release kinetics of PTX within PTX-GSSG-PEG were quantified using ultraviolet spectroscopy (UV-Vis). The size of the PTX-GSSG-PEG micelles was 83 nm, as evaluated using dynamic light scattering (DLS), and their particle size remained stable in a pH 7.4 PBS for 7 days. Moreover, the micelles could responsively degrade and release PTX in a reduced glutathione environment. The drug loading of PTX in PTX-GSSG-PEG was 13%, as determined using NMR. Furthermore, the cumulative drug release rate of PTX from the micelles reached 72.1% in a reduced glutathione environment of 5 mg/mL at 120 h. Cell viability experiments demonstrated that the PTX-GSSG-PEG micelles could induce the apoptosis of MCF-7 cells. Additionally, cell uptake showed that the micelles could distribute to the cell nuclei within 7 h. To sum up, with this glutathione-responsive paclitaxel prodrug micelle based on the endogenous molecule GSSG, it may be possible to develop novel nanomedicines in the future. |
| format | Article |
| id | doaj-art-6bb4736e7f7c4c6492fba6e88d5efa04 |
| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-6bb4736e7f7c4c6492fba6e88d5efa042025-08-20T01:55:46ZengMDPI AGPharmaceutics1999-49232024-09-01169117810.3390/pharmaceutics16091178Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer TherapyXiao Duan0Qiang Wang1Yue Wang2Xinping Liu3Manman Lu4Zhifang Li5Xuelian Jiang6Jingquan Ji7Changzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, ChinaChangzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, ChinaCentral Lab Changzhi Medical College, Changzhi Medical College, Changzhi 046000, ChinaChangzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, ChinaCentral Lab Changzhi Medical College, Changzhi Medical College, Changzhi 046000, ChinaChangzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, ChinaChangzhi Key Laboratory of Drug Molecular Design and Innovative Pharmaceutics, Shanxi Provincial Department-Municipal Key Laboratory Cultivation Base for Quality Enhancement and Utilization of Shangdang Chinese Medicinal Materials, School of Pharmacy, Changzhi Medical College, Changzhi 046000, ChinaCentral Lab Changzhi Medical College, Changzhi Medical College, Changzhi 046000, ChinaUsing an endogenous carrier is the best method to address the biocompatibility of carriers in the drug delivery field. Herein, we prepared a glutathione-responsive paclitaxel prodrug micelle based on an endogenous molecule of L-glutathione oxidized (GSSG) for cancer therapy using one-pot synthesis. The carboxyl groups in L-glutathione oxidized were reacted with the hydroxyl group in paclitaxel (PTX) using the catalysts dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Then, the amino-polyethylene glycol monomethyl ether (mPEG-NH<sub>2</sub>) was conjugated with GSSG to prepare PTX-GSSG-PEG. The structure of PTX-GSSG-PEG was characterized using infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS). The drug release kinetics of PTX within PTX-GSSG-PEG were quantified using ultraviolet spectroscopy (UV-Vis). The size of the PTX-GSSG-PEG micelles was 83 nm, as evaluated using dynamic light scattering (DLS), and their particle size remained stable in a pH 7.4 PBS for 7 days. Moreover, the micelles could responsively degrade and release PTX in a reduced glutathione environment. The drug loading of PTX in PTX-GSSG-PEG was 13%, as determined using NMR. Furthermore, the cumulative drug release rate of PTX from the micelles reached 72.1% in a reduced glutathione environment of 5 mg/mL at 120 h. Cell viability experiments demonstrated that the PTX-GSSG-PEG micelles could induce the apoptosis of MCF-7 cells. Additionally, cell uptake showed that the micelles could distribute to the cell nuclei within 7 h. To sum up, with this glutathione-responsive paclitaxel prodrug micelle based on the endogenous molecule GSSG, it may be possible to develop novel nanomedicines in the future.https://www.mdpi.com/1999-4923/16/9/1178glutathione responsivenesspaclitaxel prodrugmicellesantitumor |
| spellingShingle | Xiao Duan Qiang Wang Yue Wang Xinping Liu Manman Lu Zhifang Li Xuelian Jiang Jingquan Ji Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer Therapy Pharmaceutics glutathione responsiveness paclitaxel prodrug micelles antitumor |
| title | Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer Therapy |
| title_full | Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer Therapy |
| title_fullStr | Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer Therapy |
| title_full_unstemmed | Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer Therapy |
| title_short | Preparation of Glutathione-Responsive Paclitaxel Prodrug Based on Endogenous Molecule of L-Glutathione Oxidized for Cancer Therapy |
| title_sort | preparation of glutathione responsive paclitaxel prodrug based on endogenous molecule of l glutathione oxidized for cancer therapy |
| topic | glutathione responsiveness paclitaxel prodrug micelles antitumor |
| url | https://www.mdpi.com/1999-4923/16/9/1178 |
| work_keys_str_mv | AT xiaoduan preparationofglutathioneresponsivepaclitaxelprodrugbasedonendogenousmoleculeoflglutathioneoxidizedforcancertherapy AT qiangwang preparationofglutathioneresponsivepaclitaxelprodrugbasedonendogenousmoleculeoflglutathioneoxidizedforcancertherapy AT yuewang preparationofglutathioneresponsivepaclitaxelprodrugbasedonendogenousmoleculeoflglutathioneoxidizedforcancertherapy AT xinpingliu preparationofglutathioneresponsivepaclitaxelprodrugbasedonendogenousmoleculeoflglutathioneoxidizedforcancertherapy AT manmanlu preparationofglutathioneresponsivepaclitaxelprodrugbasedonendogenousmoleculeoflglutathioneoxidizedforcancertherapy AT zhifangli preparationofglutathioneresponsivepaclitaxelprodrugbasedonendogenousmoleculeoflglutathioneoxidizedforcancertherapy AT xuelianjiang preparationofglutathioneresponsivepaclitaxelprodrugbasedonendogenousmoleculeoflglutathioneoxidizedforcancertherapy AT jingquanji preparationofglutathioneresponsivepaclitaxelprodrugbasedonendogenousmoleculeoflglutathioneoxidizedforcancertherapy |