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A corrole nanobiologic elicits tissue-activated MRI contrast enhancement and tumor-targeted toxicity
- A corrole nanobiologic elicits tissue-activated MRI contrast enhancement and tumor-targeted toxicity
- Sims, JD[Sims, Jessica D.]; Hwang, JY[Hwang, Jae Youn]; Wagner, S[Wagner, Shawn]; Alonso-Valenteen, F[Alonso-Valenteen, Felix]; Hanson, C[Hanson, Chris]; Taguiam, JM[Taguiam, Jan Michael]; Polo, R[Polo, Richard]; Harutyunyan, I[Harutyunyan, Ira]; Karapetyan, G[Karapetyan, Gevorg]; Sorasaenee, K[Sorasaenee, Karn]; Ibrahim, A[Ibrahim, Ahmed]; Marban, E[Marban, Eduardo]; Moats, R[Moats, Rex]; Gray, HB[Gray, Harry B.]; Gross, Z[Gross, Zeev]; Medina-Kauwe, LK[Medina-Kauwe, Lali K.]
- DGIST Authors
- Hwang, JY[Hwang, Jae Youn]
- Issue Date
- Journal of Controlled Release, 217, 92-101
- Article Type
- Animal Cell; Animal Experiment; Animal Model; Animal Tissue; Cell Membranes; Contrast-Enhancing Agents; Contrast Enhancement; Contrast Medium; Controlled Study; Corrole; Corroles; Doxorubicin; Drug Delivery System; Excitation Wavelength; Female; Human; Human Cell; Magnetic Resonance Imaging; Manganese; Mitochondria; Mitochondrial Membrane Potential; Mouse; MRI; Nanoparticle; Nanoparticles; Neoplasm; Non-Human; Nuclear Magnetic Resonance Imaging; Pertuzumab; pH; Polypeptide; Polypyrroles; Priority Journal; Proteins; Systemic Deliveries; Therapeutic Efficacy; Therapeutic Modality; Tissue; Tissue Activated Magnetic Resonance Imaging Contrast Enhancement; Toxicity; Trastuzumab; Tumor-Targeting; Tumor Targeted Toxicity; Tumor Targeting; Tumors; Unclassified Drug
- 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. © 2015 Elsevier B.V. All rights reserved.
- Elsevier B.V.
- Related Researcher
Hwang, Jae Youn
MBIS(Multimodal Biomedical Imaging and System) Laboratory
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