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Controllable Synthesis of a Smart Multifunctional Nanoscale Metal−Organic Framework for Magnetic Resonance/Optical Imaging and Targeted Drug Delivery
Summary:
The authors from College of Chemistry and Chemical Engineering, Inner Mongolia University and College of Life Sciences, Inner Mongolia University developed a smart multifunctional nanoscale metal−organic framework (Fe-MIL-53-NH₂-FA-5-FAM/5-FU) with characteristics such as good biocompatibility, tumor-targeting ability, excellent imaging capabilities, and effective drug delivery, achieving promising results in the application of cancer diagnosis and therapy.
Background:
1. Metal−organic frameworks (MOFs) have advantages as drug delivery platforms, but existing ones lack tumor-targeting capability, causing toxicity to normal cells. Though nanomaterials integrating imaging and drug delivery exist, their preparation is complex, and few combine magnetic/fluorescence imaging, cell-targeting, and drug delivery in one MOF-based platform.
2. The authors proposed a simple postsynthetic surface modification method to develop a multifunctional MOF-based tumor targeting drug delivery system (DDS), which integrates diagnostic and treatment functions.
Research Content:
1. Synthesis:
The authors first synthesized Fe-MIL-53-NH₂ nanocrystalline via a low-temperature reaction of FeCl₃·6H₂O and 2-amino terephthalic acid in ethanol. Then, 5-fluorouracil (5-FU) was loaded into it. Subsequently, folic acid (FA) and 5-carboxyfluorescein (5-FAM) were conjugated to the 5-FU-loaded Fe-MIL-53-NH₂ using N-(3-(dimethylamino)propyl)-N-ethylcarbodiimide hydrochloride (EDC) as a dehydrating agent, obtaining Fe-MIL-53-NH₂-FA-5-FAM/5-FU.
2. Characterizations:
1) BET: Fe-MIL-53-NH₂ nanocomposite has a BET surface area up to 198 m²/g.
2) SEM tests: The particle size of Fe-MIL-53-NH₂ can be tuned from 120 nm to 1 μm by changing reactant concentrations, and 120 nm was chosen for further modification.
3) Other tests: XRD confirmed the crystallinity and structure of the materials; FTIR spectra verified the successful conjugation of FA, 5-FAM, and loading of 5-FU; TGA showed larger weight loss for the DDS due to decomposition of loaded components; fluorescence spectra indicated the DDS has green emission suitable for imaging; MRI tests showed high relaxivity (r₂=18.8 mM⁻¹s⁻¹) for T₂-weighted imaging.
3. Application:
- Cytotoxicity study: Fe-MIL-53-NH₂-FA-5-FAM has good biocompatibility. The DDS shows dose-dependent toxicity to MGC-803 cancer cells, inducing 45% death at 200 μg/mL, but little toxicity to normal HASMC cells.
- Cellular uptake study: The DDS specifically targets FA-positive MGC-803 cells with strong fluorescence, but not FA-negative HASMC cells or MGC-803 cells without FA conjugation.
- In vivo MRI: Intratumoral injection of the DDS enhances tumor contrast in T₂-weighted images.
- Biodistribution: The DDS accumulates in various organs, with the highest intensity in the liver, and is stable in physiological conditions.
- Drug release: 5-FU is released sustainably, with faster release in acidic pH (pH 5) and lasting over 20 h.
4. Mechanism:
The targeting ability is due to FA's affinity with folate receptors overexpressed on cancer cells. The MRI capability comes from Fe in the MOF, which shortens T₂ relaxation time via dipolar interaction with water protons. The fluorescence imaging is from 5-FAM. Sustained drug release is attributed to the MOF's pores and diffusion, with faster release in acidic environments possibly due to slight MOF dissolution.
Outlook:
This research successfully develops a multifunctional MOF-based DDS through a simple method, integrating dual-mode imaging and targeted drug delivery. It provides a new platform for cancer theranostics, showing great potential in biomedical applications and laying a foundation for further development of MOF-based drug delivery systems.
Controllable Synthesis of a Smart Multifunctional Nanoscale Metal−Organic Framework for Magnetic Resonance/Optical Imaging and Targeted Drug Delivery
Authors: Xuechuan Gao, Manjue Zhai, Weihua Guan, Jingjuan Liu, Zhiliang Liu, Alatangaole Damirin
DOI: 10.1021/acsami.6b14795
Link: https://pubs.acs.org/doi/10.1021/acsami.6b14795
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