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Anticancer effects of silymarin-loaded ACA-HA/sulfonamide IR-MOF nanoplatform in CT-26 xenograft model
Sedigheh Alavinia1, Ramin Ghorbani-Vaghei2, Rasool Haddadi3
1Department of Organic Chemistry, Faculty of Chemistry and Petroleum Sciences, Bu-Ali Sina University, 6517838683 Hamadan, Iran.
Abstract:
Silymarin, a herbal compound with antioxidant and anti-inflammatory properties, has shown potential in inhibiting colon cancer cell growth. However, its clinical application is hindered by poor bioavailability. This study introduces a novel metal-organic framework, Sul-IRMOF, modified with 6-aminocaproic acid (ACA) and hyaluronic acid (HA) to create Sul-IRMOF-ACA-HA, which enables targeted drug delivery via HA receptors. Histological staining, biochemical analyses, and flow cytometry revealed that Sul-IRMOF-ACA-HA@Sily significantly enhances cytotoxicity against CT-26 cells compared to pure silymarin. According to oxidative stress markers, Sul-IRMOF-ACA-HA@Sily significantly reduced total thiol and glutathione (GSH) content compared to the control (p < 0.001) and silymarin (p < 0.001). Catalase (CAT) and superoxide dismutase (SOD) activities were significantly reduced in all treatment groups (p < 0.001), with Sul-IRMOF-ACA-HA@Sily showing the most pronounced effects (p < 0.001 vs. silymarin). Additionally, malondialdehyde (MDA) and nitric oxide (NO) levels were significantly elevated in the silymarin and Sul-IRMOF-ACA-HA@Sily groups compared to the control (p < 0.001), with Sul-IRMOF-ACA-HA@Sily further increasing both markers compared to silymarin (p < 0.001). The synergistic design of ACA, HA, and Sul-IRMOF offers a promising strategy to overcome silymarin's bioavailability limitations, positioning Sul-IRMOF-ACA-HA@Sily as a novel therapeutic candidate for colorectal cancer.
Insights
This study developed Sul-IRMOF-ACA-HA@Sily, a novel drug delivery system that enhances silymarin
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Silymarin, a natural compound, exhibits antioxidant and anti-inflammatory properties beneficial for colon cancer treatment.
- Poor bioavailability limits silymarin's clinical efficacy in cancer therapy.
- Targeted drug delivery systems are crucial for improving cancer treatment outcomes.
Purpose of the Study:
- To develop a novel metal-organic framework (MOF) based drug delivery system for silymarin.
- To enhance silymarin's bioavailability and targeted delivery for colorectal cancer treatment.
- To evaluate the efficacy of the novel system against colon cancer cells.
Main Methods:
- Synthesis of a modified MOF, Sul-IRMOF, incorporating 6-aminocaproic acid (ACA) and hyaluronic acid (HA).
- Encapsulation of silymarin into the modified MOF to create Sul-IRMOF-ACA-HA@Sily for targeted delivery.
- In vitro evaluation of cytotoxicity, oxidative stress markers (total thiol, GSH, CAT, SOD, MDA, NO) using histological staining, biochemical analyses, and flow cytometry on CT-26 colon cancer cells.
Main Results:
- Sul-IRMOF-ACA-HA@Sily demonstrated significantly enhanced cytotoxicity against CT-26 cells compared to silymarin alone.
- The novel system significantly modulated oxidative stress markers, reducing GSH and CAT/SOD activities while increasing MDA and NO levels.
- The targeted delivery mechanism via HA receptors was successfully implemented, improving silymarin's therapeutic potential.
Conclusions:
- The synergistic combination of ACA, HA, and Sul-IRMOF effectively overcomes silymarin's bioavailability issues.
- Sul-IRMOF-ACA-HA@Sily represents a promising novel therapeutic candidate for colorectal cancer treatment.
- This nanotechnology-based approach offers a viable strategy for improving the efficacy of natural compounds in cancer therapy.
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