Related Experiment Video
Updated: Mar 8, 2026
Introduction to the Ultrasound Targeted Microbubble Destruction Technique
Published on: June 12, 2011
Ultrasound targeted microbubble destruction-assisted mesoporous silicon delivery of dexamethasone inhibits ulcerative
Kai Kang1, Zimo Zhou2, Yueting Zhang3
1Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
Aims:
This study aims to elucidate the role of acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated ferroptosis in ulcerative colitis (UC). Furthermore, we evaluated the therapeutic efficacy of dexamethasone (DEX)-loaded hollow mesoporous silica nanoparticles (HMSN@DEX) in combination with ultrasound-targeted microbubble destruction (UTMD) to enhance targeted delivery and achieve synergistic treatment effects.
Materials And Methods:
The therapeutic performance of HMSN@DEX was assessed using cell cultures and mouse models. UTMD was employed to facilitate targeted delivery, with the underlying ACSL4-mediated ferroptosis mechanism analyzed across multiple biological levels.
Key Findings:
Our research shows that inhibition of ACSL4 prevents ferroptosis death of intestinal epithelial cells and attenuates experimental colitis in mice. Mechanistically, Metadherin (MTDH) regulate the ubiquitination of ACSL4 by binding with Lys37 thus interfere the interaction between ACSL4 and MARCHF6, while simultaneously activating NF-κB signaling. Moreover, MTDH knockdown ameliorate ferroptosis in IECs induced by erastin and this effect can be counteract by ACSL4-WT. When the lys37 was mutated with K37A, ACSL4-K37A cannot achieve this effect. Further, the combination of UTMD and HMSN@DEX possess better colonic drug accumulation in the colon of mice with colitis. In both cellular and murine models of colitis, the UTMD+HMSN@DEX has better therapeutics effect than free dexamethasone or HMSN@DEX alone by regulating the MTDH/ACSL4/NF-κB pathway.
Significance:
Our research reveals the critical role of the MTDH/ACSL4/NF-κB signaling pathway in regulating intestinal ferroptosis. The combination of UTMD and HMSN@DEX achieved the most significant attenuation in colitis among the three delivery strategies.
Insights
This study reveals that targeting acyl-CoA synthetase long-chain family member 4 (ACSL4) and ferroptosis is key in ulcerative colitis (UC). Combining ultrasound-targeted microbubble destruction with dexamethasone nanoparticles offers a potent therapeutic strategy for colitis.
Area of Science:
- Gastroenterology
- Nanomedicine
- Molecular Biology
Background:
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
- Ferroptosis, a regulated form of cell death, plays a significant role in the pathogenesis of UC.
- Acyl-CoA synthetase long-chain family member 4 (ACSL4) is implicated in ferroptosis, but its precise role in UC requires further elucidation.
Purpose of the Study:
- To investigate the role of ACSL4-mediated ferroptosis in UC.
- To evaluate the therapeutic efficacy of dexamethasone (DEX)-loaded hollow mesoporous silica nanoparticles (HMSN@DEX) combined with ultrasound-targeted microbubble destruction (UTMD) for targeted drug delivery and synergistic treatment in UC.
Main Methods:
- Cell cultures and mouse models of colitis were used to assess therapeutic performance.
- UTMD was employed to enhance targeted delivery of HMSN@DEX.
- The mechanism of ACSL4-mediated ferroptosis was analyzed, including the role of Metadherin (MTDH) and NF-κB signaling.
Main Results:
- Inhibition of ACSL4 prevented ferroptosis and attenuated experimental colitis in mice.
- MTDH regulates ACSL4 ubiquitination, affecting its interaction with MARCHF6 and activating NF-κB signaling.
- The combination of UTMD and HMSN@DEX demonstrated superior colonic drug accumulation and therapeutic effects in both cellular and murine colitis models compared to free DEX or HMSN@DEX alone.
Conclusions:
- The MTDH/ACSL4/NF-κB signaling pathway is critical in regulating intestinal ferroptosis in UC.
- The combined UTMD and HMSN@DEX delivery strategy achieved the most significant attenuation of colitis, highlighting its therapeutic potential.
More Related Videos
14:10Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation
Published on: December 15, 2010
07:45Ultrasound-guided Intracardiac Injection of Human Mesenchymal Stem Cells to Increase Homing to the Intestine for Use in Murine Models of Experimental Inflammatory Bowel Diseases
Published on: September 1, 2017
Related Concept Videos
01:29Drugs for Treatment of Ulcerative Colitis in IBD
01:21Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
01:20Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
01:26Peptic Ulcer Disease IV: Management
The therapeutic approach involves ensuring adequate rest, implementing drug therapy, promoting smoking cessation, making dietary modifications, and emphasizing long-term follow-up care.
Pharmacological management
The prevailing therapy for peptic ulcers involves a combination of managing the patient's current...