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A Biocompatible NMOF-Based Drug Delivery System Designed for the Sustained and Controlled Release via pH-Responsive
Mohammad Bereyhi1, Rouholah Zare-Dorabei1, Vahid Safarifard1
1Research Laboratory of Spectrometry & Micro and Nano Extraction, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran.
Abstract:
Cancer is among the most challenging diseases to manage, affecting millions of lives today. Numerous treatment approaches have been employed to combat cancer, each with its own limitations. One approach involves using anticancer medications that, regrettably, come with significant side effects. One reason for these issues is the lack of specificity in anticancer drugs, which can harm healthy tissues alongside targeted cancer cells. In this research, our goal is to minimize side effects and enhance drug effectiveness through advanced drug delivery techniques. The metal-organic framework (MOF) was swiftly created at the nanoscale using solvothermal synthesis. The NMOF-74 particles measure is nanometric in size and have a surface area of 950 m2 g-1. After the introduction of 5-fluorouracil, a coating of poly(acrylic acid) polymer was applied to the nanocarrier. The biocompatible nanocarrier demonstrated a strong ability to absorb the drug. The bioresorbable nanocarrier gradually and evenly released 97.9% of the drug in the simulated environment. This indicates that 5-FLU/NMOF-74 released the drug in a controlled and pH-responsive manner. The robustness of the compatible nanocarrier was tested across various pH levels and was found to remain stable at pH 1.2 for up to 72 h. The toxicity evaluation performed over a 24 h period on the MCF-7 cell line at various concentrations demonstrates that the compatible nanocarrier performs significantly better than the free drug regarding its impact on breast cancer cells.
Insights
This study developed a novel nanocarrier (NMOF-74) for 5-fluorouracil (5-FU) cancer drug delivery. The nanocarrier enhances drug efficacy and reduces side effects by providing controlled, pH-responsive release and showing lower toxicity to healthy cells.
Area of Science:
- Materials Science
- Nanotechnology
- Biomedical Engineering
Background:
- Cancer treatment faces challenges with drug side effects due to lack of specificity.
- Anticancer drugs can harm healthy tissues, necessitating advanced delivery systems.
- Improving drug effectiveness and minimizing toxicity are key goals in cancer therapy.
Purpose of the Study:
- To develop a biocompatible and bioresorbable nanocarrier for enhanced 5-fluorouracil (5-FU) delivery.
- To create a nanoscale metal-organic framework (MOF) for controlled and targeted drug release.
- To evaluate the efficacy and safety of the novel nanocarrier system.
Main Methods:
- Synthesized nanoscale NMOF-74 via solvothermal methods, characterized by high surface area (950 m² g⁻¹).
- Loaded 5-fluorouracil (5-FU) onto NMOF-74 and coated with poly(acrylic acid) to create 5-FLU/NMOF-74.
- Assessed drug loading, release kinetics (pH-responsive), nanocarrier stability (pH 1.2 for 72h), and in vitro toxicity on MCF-7 cells.
Main Results:
- The 5-FLU/NMOF-74 nanocarrier exhibited efficient drug absorption and sustained release of 97.9% in simulated environments.
- The nanocarrier demonstrated controlled and pH-responsive drug release, crucial for targeted delivery.
- Stability was confirmed at low pH (1.2) for 72 hours, and toxicity assays showed superior performance compared to free 5-FU against breast cancer cells.
Conclusions:
- The developed 5-FLU/NMOF-74 nanocarrier offers a promising platform for improved cancer chemotherapy.
- This advanced drug delivery system enhances 5-FU efficacy while mitigating side effects through controlled release and reduced toxicity.
- The nanocarrier's stability and biocompatibility support its potential clinical application in cancer treatment.

