Porosity Modification in MOF Nanocarriers for pH-Responsive Drug Delivery in Cancer Therapy
Creators
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1.
Iran University of Science and Technology
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2.
Western University
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3.
Pasteur Institute of Iran
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4.
Sharif University of Technology
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5.
K.N.Toosi University of Technology
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6.
California Institute of Technology
Abstract
Metal–organic frameworks (MOFs) have emerged as promising nanocarriers for targeted drug delivery, particularly in cancer therapy. Introducing structural defects into MOFs significantly enhances their drug-loading capacity and release efficiency. This study explores porosity modification through defect-engineered MOF-808 nanocarriers, synthesized via a mixed-ligand strategy, to enhance the stability, pH-responsiveness, and drug delivery efficiency for cancer therapy. The modified MOF-808 variants were loaded with 5-fluorouracil (5-FU) in ethanol and water to optimize the drug loading capacity (DLC) and drug release efficiency (DLE). Among them, MOF-808-15% demonstrated a drug release of 57.7% at pH 7.4 and 70.8% at pH 5.5, showing a 22.7% increase under acidic conditions, which is ideal for pH-responsive drug delivery. Density functional theory (DFT) calculations revealed a strong adsorption energy (−1.13 eV) between MOF-808 and 5-FU, confirming effective drug-framework interactions. Additionally, a biodegradable polydopamine (PDA) coating enhanced the stability and enabled controlled drug release in acidic environments. In the 5-FU@MOF-808-15%/PDA system, 64.4% of the drug was released at pH 5.5, marking a 21.97% improvement compared with neutral conditions. Cytotoxicity assays on MCF-7 cells showed 77.65% inhibition, comparable to free 5-FU (80.4%) at 400 μg/mL. These findings demonstrate that precise defect engineering in MOFs can yield highly efficient and biocompatible drug nanocarriers, paving the way for advanced controlled-release cancer therapies.
Copyright and License
© 2025 American Chemical Society.
Acknowledgement
Our gratitude goes out to the Iran University of Science and Technology (IUST) for providing us with various facilities and materials. In this study, no specific grants were received from public, commercial, or nonprofit funding agencies.
Contributions
A.K.: conceptualization, methodology, software, conceived and designed the experiments, validation, formal analysis, investigation, resources, data curation, and writing─review and editing. H.A.M.A.: software, validation, formal analysis, investigation, resources, visualization, writing─review and editing. M.H.A.: software, validation, formal analysis, investigation, resources, visualization, and writing─review and editing. M.T.: software, DFT, validation, investigation, resources, visualization, and writing─review and editing. H.B.: conceptualization, methodology, formal analysis, investigation, and writing─review and editing. S.K.: methodology, formal analysis, investigation, and writing─review and editing. F.Z.: conceptualization, methodology, formal analysis, investigation, and writing─review and editing. E.T.: conceptualization, methodology, formal analysis, investigation, and writing─review and editing. G.S.F.: software, validation, formal analysis, investigation, resources, visualization, and writing─review and editing. F.M.: supervision, funding acquisition, methodology, conceived and designed the experiments, formal analysis, investigation, resources, data curation, and writing─original draft. S.R.: investigation, resources, funding acquisition, methodology, visualization, and writing─review and editing. W.A.G.: funding acquisition, methodology, conceived and designed the experiments, data curation, and writing─review and editing.
Supplemental Material
UV–vis spectra and calibration curves of 5-FU in D.I. water and PBS, FTIR spectra of 5-FU@MOF-808-A/PDA composites, DLS size distribution of MOF-808 particles, in vitro drug release UV–vis spectra at pH 7.4 and 5.5, and visual comparison of MOF-808 before and after synthesis (PDF)
Files
mt5c00838_si_001.pdf
Files
(1.3 MB)
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Additional details
Identifiers
- PMID
- 40830077
Related works
- Describes
- 40830077 (PMID)
- Is supplemented by
- Supplemental Material: https://pubs.acs.org/doi/suppl/10.1021/acsabm.5c00838/suppl_file/mt5c00838_si_001.pdf (URL)
Dates
- Accepted
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2025-08-08
- Available
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2025-08-19Published online