Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil
Abstract
:1. Introduction
2. Results
2.1. In vitro Studies: Drug Release Profile, Cytotoxicity Assay, and Cellular Uptake Efficiency in FR Cells
2.2. Antitumor Efficacy in Mice Hepatoma Model
2.3. Molecular Docking and Molecular Dynamics Simulations
3. Discussion
4. Materials and Methods
4.1. Chemistry
4.2. Folate Prodrug (FA-PEG-5-FU) Synthesis
4.3. In Vitro Drug Release
4.4. Cytotoxicity Assays Study (In Vitro)
4.5. Cellular Uptake Efficiency in FR+ Cells
4.6. Antitumor Efficacy on Mice Hepatoma
4.7. Molecular Docking
4.8. Molecular Dynamics Simulations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Tissue | Saline | FA-PEG-5-FU | 5-FU |
---|---|---|---|
Heart | 0.4406 ± 0.34 | 0.4310 ± 0.43 | 0.4246 ± 0.41 |
Liver | 5.5436 ± 0.27 | 6.0516 ± 1.03 | 5.3760 ± 0.96 |
Spleen | 1.1261 ± 0.321 | 1.2616 ± 0.44 | 1.1976 ± 0.57 |
Lung | 0.9816 ± 0.226 | 0.9156 ± 0.24 | 1.616 ± 0.50 |
Kidney | 1.4616 ± 0.131 | 1.3177 ± 0.08 | 1.4361 ± 0.12 |
Brain | 1.3561 ± 0.12 | 1.3161 ± 0.21 | 1.4116 ± 0.30 |
Thymus | 0.1927 ± 0.08 | 0.2716 ± 0.07 | 0.2215 ± 0.15 |
Tumor | 7.0817 ± 1.860 | 3.3917 ± 1.22 | 4.9476 ± 2.31 |
AD | ΔEvdw | ΔEele | ΔEMM | ΔGp | ΔGnp | ΔGsol | ΔGtol | |
---|---|---|---|---|---|---|---|---|
FA | −7.1 | −63.71 | −79.25 | −142.96 | 97.12 | −6.89 | 90.23 | −52.73 |
FA-PEG-5-FU | −9.6 | −74.03 | −89.92 | −163.95 | 107.7 | −8.95 | 98.75 | −65.2 |
Drug Delivery Carriers | Drugs Loaded | Reference |
---|---|---|
Chitosan-PEG-Folate loaded 5-FU | 5-Fluorouracil | [55] |
Folate-poly(ethylene glycol)-poly(propylene succinate) nanoparticles | Paclitaxel | [76] |
Folate-modified lipid-polymer hybrid nanoparticles | Paclitaxel | [77] |
Folate-polyethyleneglycol-distearoylphosphatidylethanolamine (folate-PEG-DSPE) loaded DOX | Doxorubicin | [56] |
Polymeric mixed micelles of poly(L-histidine)/PEG and poly(L-lactic acid) (PLLA) conjugate of folate | Adriamycin | [78] |
Folic acid conjugated nanoparticles | Docetaxel | [79] |
Folic acid-modified liposome-5-FU | 5-Fluorouracil | [80] |
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Sarwar, S.; Abdul Qadir, M.; Alharthy, R.D.; Ahmed, M.; Ahmad, S.; Vanmeert, M.; Mirza, M.U.; Hameed, A. Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil. Molecules 2022, 27, 1780. https://doi.org/10.3390/molecules27061780
Sarwar S, Abdul Qadir M, Alharthy RD, Ahmed M, Ahmad S, Vanmeert M, Mirza MU, Hameed A. Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil. Molecules. 2022; 27(6):1780. https://doi.org/10.3390/molecules27061780
Chicago/Turabian StyleSarwar, Shabnam, Muhammad Abdul Qadir, Rima D. Alharthy, Mahmood Ahmed, Saghir Ahmad, Michiel Vanmeert, Muhammad Usman Mirza, and Abdul Hameed. 2022. "Folate Conjugated Polyethylene Glycol Probe for Tumor-Targeted Drug Delivery of 5-Fluorouracil" Molecules 27, no. 6: 1780. https://doi.org/10.3390/molecules27061780