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A corrole nanobiologic elicits tissue-activated MRI contrast enhancement and tumor-targeted toxicity
Jessica D Sims1, Jae Youn Hwang2, Shawn Wagner3
1Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Abstract:
Water-soluble corroles with inherent fluorescence can form stable self-assemblies with tumor-targeted cell penetration proteins, and have been explored as agents for optical imaging and photosensitization of tumors in pre-clinical studies. However, the limited tissue-depth of excitation wavelengths limits their clinical applicability. To examine their utility in more clinically-relevant imaging and therapeutic modalities, here we have explored the use of corroles as contrast enhancing agents for magnetic resonance imaging (MRI), and evaluated their potential for tumor-selective delivery when encapsulated by a tumor-targeted polypeptide. We have found that a manganese-metallated corrole exhibits significant T1 relaxation shortening and MRI contrast enhancement that is blocked by particle formation in solution but yields considerable MRI contrast after tissue uptake. Cell entry but not low pH enables this. Additionally, the corrole elicited tumor-toxicity through the loss of mitochondrial membrane potential and cytoskeletal breakdown when delivered by the targeted polypeptide. The protein-corrole particle (which we call HerMn) exhibited improved therapeutic efficacy compared to current targeted therapies used in the clinic. Taken together with its tumor-preferential biodistribution, our findings indicate that HerMn can facilitate tumor-targeted toxicity after systemic delivery and tumor-selective MR imaging activatable by internalization.
Insights
This study explores manganese-metallated corroles for MRI contrast enhancement and tumor-targeted therapy. These novel agents show promise for improved tumor imaging and treatment delivery.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Medical Imaging
Background:
- Water-soluble corroles are fluorescent and used in pre-clinical optical imaging and photosensitization.
- Limited tissue penetration of excitation wavelengths restricts their clinical use.
- Corroles offer potential for advanced imaging and therapeutic applications.
Purpose of the Study:
- To evaluate corroles as MRI contrast agents.
- To assess tumor-selective delivery using a targeted polypeptide.
- To investigate the therapeutic potential of protein-corrole assemblies.
Main Methods:
- Manganese-metallated corroles were synthesized and characterized.
- Tumor-targeted polypeptides were used to encapsulate corroles.
- MRI contrast enhancement and cellular uptake mechanisms were studied.
- In vitro cytotoxicity and therapeutic efficacy were evaluated.
Main Results:
- Manganese corroles significantly shortened T1 relaxation, enhancing MRI contrast post-tissue uptake.
- Cellular entry, not low pH, enabled MRI contrast enhancement.
- The protein-corrole particle (HerMn) demonstrated tumor-selective toxicity via mitochondrial and cytoskeletal disruption.
- HerMn showed improved therapeutic efficacy compared to existing targeted therapies.
Conclusions:
- HerMn facilitates tumor-targeted toxicity and tumor-selective MRI after systemic delivery and internalization.
- Corrole-based nanoparticles represent a promising platform for combined cancer imaging and therapy.
- Further clinical translation is warranted based on pre-clinical efficacy and biodistribution data.
