Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil
A targeted delivery system is primarily intended to carry a potent anticancer drug to specific tumor sites within the bodily tissues. In the present study, a carrier system has been designed using folic acid (FA), bis-amine polyethylene glycol (PEG), and an anticancer drug, 5-fluorouracil (5-FU). FA...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/6/1780 |
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| author | Shabnam Sarwar Muhammad Abdul Qadir Rima D. Alharthy Mahmood Ahmed Saghir Ahmad Michiel Vanmeert Muhammad Usman Mirza Abdul Hameed |
| author_facet | Shabnam Sarwar Muhammad Abdul Qadir Rima D. Alharthy Mahmood Ahmed Saghir Ahmad Michiel Vanmeert Muhammad Usman Mirza Abdul Hameed |
| author_sort | Shabnam Sarwar |
| collection | DOAJ |
| description | A targeted delivery system is primarily intended to carry a potent anticancer drug to specific tumor sites within the bodily tissues. In the present study, a carrier system has been designed using folic acid (FA), bis-amine polyethylene glycol (PEG), and an anticancer drug, 5-fluorouracil (5-FU). FA and PEG were joined via an amide bond, and the resulting FA-PEG-NH<sub>2</sub> was coupled to 5-FU producing folate-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU). Spectroscopic techniques (UV-Vis, <sup>1</sup>HNMR, FTIR, and HPLC) were used for the characterization of products. Prodrug (FA-PEG-5-FU) was analyzed for drug release profile (in vitro) up to 10 days and compared to a standard anticancer drug (5-FU). Folate conjugate was also analyzed to study its folate receptors (FR) mediated transport and in vitro cytotoxicity assays using HeLa cancer cells/Vero cells, respectively, and antitumor activity in tumor-bearing mice models. Folate conjugate showed steady drug release patterns and improved uptake in the HeLa cancer cells than Vero cells. Folate conjugate treated mice group showed smaller tumor volumes; specifically after the 15th day post-treatment, tumor sizes were decreased significantly compared to the standard drug group (5-FU). Molecular docking findings demonstrated importance of Trp138, Trp140, and Lys136 in the stabilization of flexible loop flanking the active site. The folic acid conjugated probe has shown the potential of targeted drug delivery and sustained release of anticancer drug to tumor lesions with intact antitumor efficacy. |
| first_indexed | 2024-03-09T13:11:23Z |
| format | Article |
| id | doaj.art-353b6be3fb6f4323ab0ab2db5dd5816e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T13:11:23Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-353b6be3fb6f4323ab0ab2db5dd5816e2023-11-30T21:41:03ZengMDPI AGMolecules1420-30492022-03-01276178010.3390/molecules27061780Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-FluorouracilShabnam Sarwar0Muhammad Abdul Qadir1Rima D. Alharthy2Mahmood Ahmed3Saghir Ahmad4Michiel Vanmeert5Muhammad Usman Mirza6Abdul Hameed7School of Chemistry, University of the Punjab, Lahore 54590, PakistanSchool of Chemistry, University of the Punjab, Lahore 54590, PakistanChemistry Department, Faculty of Science and Arts, King Abdulaziz University, Rabigh 21911, Saudi ArabiaDepartment of Chemistry, Division of Science and Technology, University of Education, College Road, Lahore 54770, PakistanSchool of Chemistry, University of the Punjab, Lahore 54590, PakistanMedicinal Chemistry, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, BelgiumMedicinal Chemistry, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, BelgiumDepartment of Chemistry, University of Sahiwal, Sahiwal 57000, PakistanA targeted delivery system is primarily intended to carry a potent anticancer drug to specific tumor sites within the bodily tissues. In the present study, a carrier system has been designed using folic acid (FA), bis-amine polyethylene glycol (PEG), and an anticancer drug, 5-fluorouracil (5-FU). FA and PEG were joined via an amide bond, and the resulting FA-PEG-NH<sub>2</sub> was coupled to 5-FU producing folate-polyethylene glycol conjugated 5-fluorouracil (FA-PEG-5-FU). Spectroscopic techniques (UV-Vis, <sup>1</sup>HNMR, FTIR, and HPLC) were used for the characterization of products. Prodrug (FA-PEG-5-FU) was analyzed for drug release profile (in vitro) up to 10 days and compared to a standard anticancer drug (5-FU). Folate conjugate was also analyzed to study its folate receptors (FR) mediated transport and in vitro cytotoxicity assays using HeLa cancer cells/Vero cells, respectively, and antitumor activity in tumor-bearing mice models. Folate conjugate showed steady drug release patterns and improved uptake in the HeLa cancer cells than Vero cells. Folate conjugate treated mice group showed smaller tumor volumes; specifically after the 15th day post-treatment, tumor sizes were decreased significantly compared to the standard drug group (5-FU). Molecular docking findings demonstrated importance of Trp138, Trp140, and Lys136 in the stabilization of flexible loop flanking the active site. The folic acid conjugated probe has shown the potential of targeted drug delivery and sustained release of anticancer drug to tumor lesions with intact antitumor efficacy.https://www.mdpi.com/1420-3049/27/6/1780folic acidvectorHeLa cellhepatoma micemolecular dynamics simulations |
| spellingShingle | Shabnam Sarwar Muhammad Abdul Qadir Rima D. Alharthy Mahmood Ahmed Saghir Ahmad Michiel Vanmeert Muhammad Usman Mirza Abdul Hameed Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil Molecules folic acid vector HeLa cell hepatoma mice molecular dynamics simulations |
| title | Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil |
| title_full | Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil |
| title_fullStr | Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil |
| title_full_unstemmed | Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil |
| title_short | Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil |
| title_sort | folate conjugated polyethylene glycol probe for tumor targeted drug delivery of 5 fluorouracil |
| topic | folic acid vector HeLa cell hepatoma mice molecular dynamics simulations |
| url | https://www.mdpi.com/1420-3049/27/6/1780 |
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