Revolutionizing Cancer Care with Dual-Function MRI Agents
New York University Abu Dhabi (NYUAD) researchers have unveiled a groundbreaking class of smart molecules designed to simultaneously detect and treat cancer, marking a significant advancement in theranostic technologies. These manganese-based agents, featuring intricate interlocked structures like trefoil knots and Borromean rings, activate selectively in the acidic environment of tumors, releasing ions that brighten MRI images while inducing cell death in malignant tissues.
This innovation addresses longstanding limitations in cancer diagnostics and therapy, particularly for aggressive brain cancers such as glioblastoma multiforme (GBM), where early detection and precise targeting are critical. Traditional magnetic resonance imaging (MRI) relies on gadolinium-based contrast agents (GBCAs) for enhanced visualization, but these can deposit in tissues, posing risks like nephrogenic systemic fibrosis in patients with kidney impairment. The NYUAD molecules offer a safer alternative, leveraging the body's natural manganese processing pathways.
The Science Behind Supramolecular Theranostics
Supramolecular chemistry, the field pioneered by the Trabolsi Research Group at NYUAD, involves assembling molecules through non-covalent interactions to create complex architectures with tailored properties. Led by Professor Ali Trabolsi, the team, including lead researcher Farah Benyettou and synthesizer Thirumurugan Prakasam, engineered three manganese-templated structures: Mn-[2]catenate, Mn-trefoil knot (Mn-TK), and Mn-Borromean rings (Mn-BR).
These structures are stable at physiological pH (7.4) due to their electropositive, lipophilic nature, ensuring kinetic inertness in healthy tissues. In tumors, where pH drops to 6.5-6.8, the coordination framework disassembles, liberating Mn²⁺ ions. This process enhances T1 relaxivity—the measure of MRI contrast efficiency—with Mn-BR achieving 10.1 mM⁻¹ s⁻¹ and Mn-TK 6.8 mM⁻¹ s⁻¹ at 3 Tesla, surpassing standard Gd-DTPA.
- Synthesis: Microwave-assisted assembly of manganese with organic ligands forms topological knots and rings.
- Activation: Acidic pH triggers disassembly.
- Imaging: Mn²⁺ shortens T1 relaxation time, producing bright signals.
- Therapy: Ion release generates reactive oxygen species (ROS), leading to caspase-dependent apoptosis.
In vitro studies on U251-MG glioblastoma cells demonstrated IC₅₀ values of 3.0 μM for Mn-BR and 5.6 μM for Mn-TK, outperforming cisplatin (12.7 μM), with selectivity indices exceeding 9.4 and 3.9 respectively against normal HEK-293 cells.
Overcoming the Blood-Brain Barrier Challenge
Glioblastoma, the most common malignant brain tumor, presents unique hurdles due to the blood-brain barrier (BBB), which shields the brain but blocks most therapeutics. NYUAD's agents demonstrate exceptional BBB permeability via adsorptive-mediated transcytosis, accumulating specifically in tumors. In orthotopic GBM models, they provided persistent MRI enhancement superior to Gd agents, enabling real-time monitoring and targeted therapy.
In the UAE, brain tumors constitute about 2.9% of cancers, with GBM accounting for 11.6-18.8% of cases, predominantly affecting expatriates (72% of diagnoses). Mean age at diagnosis is 33.5 years, underscoring the need for innovative tools in a young, diverse population.detailed UAE brain tumor epidemiology.
Advantages Over Conventional Contrast Agents
Gadolinium agents dominate MRI but carry risks; linear GBCAs deposit in brain tissue, macrocyclic ones are safer but costly. Manganese, an essential trace element, is excreted via bile without retention issues. NYUAD's pH-responsive design minimizes off-target effects, enhancing safety for repeated scans.
| Agent | r1 Relaxivity (3T) | Safety Profile | Therapeutic Function |
|---|---|---|---|
| Gd-DTPA | ~4 mM⁻¹ s⁻¹ | Retention risk | No |
| Mn-DPDP | ~2 mM⁻¹ s⁻¹ | Better excretion | No |
| Mn-BR (NYUAD) | 10.1 mM⁻¹ s⁻¹ | pH-selective, natural clearance | Yes |
This table highlights the superior performance of NYUAD agents.
Trabolsi Lab's Role in UAE Research Excellence
Professor Ali Trabolsi's group at NYUAD excels in supramolecular assemblies for healthcare, from drug delivery to water harvesting. This JACS publication (DOI: 10.1021/jacs.5c19016), dated April 1, 2026, exemplifies UAE's rising research prowess. Collaborations with NYUAD's Core Technology Platforms bolstered imaging and in vivo validation.
UAE universities like Abu Dhabi University (ADU) recently launched a Cancer Research Institute, complementing NYUAD's efforts in personalized medicine.
Photo by Mathilde Cureau on Unsplash
In Vivo Efficacy and Biodistribution
Subcutaneous U251-MG xenografts showed Mn-TK and Mn-BR reducing tumor volume and weight, with histological evidence of apoptosis. Biodistribution confirmed tumor specificity, rapid clearance, and low organ accumulation. Orthotopic models validated BBB crossing and sustained contrast.
- Tumor Mn uptake: 5-10x higher than normal tissues.
- Systemic toxicity: Minimal (LD50 high).
- Clearance: Primarily hepatobiliary.
Implications for UAE Healthcare
With cancer as UAE's third leading cause of death, innovations like these align with Vision 2031's health goals. NYUAD's work could reduce GBM mortality, where 5-year survival is <10% globally. Integration into clinical trials at facilities like Cleveland Clinic Abu Dhabi is anticipated.
Future Directions and Clinical Translation
Benyettou notes, “Our goal was to create materials that allow doctors to see cancer clearly and treat it at the same time.” Next steps include optimization for other cancers, large-animal studies, and FDA-equivalent approvals. Partnerships with UAE health authorities could accelerate theranostic adoption.
Access the full study here.
UAE's Growing Leadership in Oncology Research
Besides NYUAD, Khalifa University advances RF-GPT AI models, and ADU's new institute focuses on translational cancer care. These efforts position UAE as a hub for precision oncology in the MENA region.
Challenges and Ethical Considerations
While promising, scalability, long-term safety, and regulatory hurdles remain. Supramolecular agents must ensure no immunogenicity. UAE's robust ethics frameworks, via NYUAD's PHRC, support responsible development.
Photo by Phillip Glickman on Unsplash
Actionable Insights for Researchers and Clinicians
For UAE academics, collaborate via NYUAD platforms. Clinicians: Monitor trials for Mn-based theranostics. Students: Explore supramolecular chemistry programs at NYUAD or Khalifa University.
