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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 CellAnimal ExperimentAnimal ModelAnimal TissueCell MembranesContrast-Enhancing AgentsContrast EnhancementContrast MediumControlled StudyCorroleCorrolesDoxorubicinDrug Delivery SystemExcitation WavelengthFemaleHumanHuman CellMagnetic Resonance ImagingManganeseMitochondriaMitochondrial Membrane PotentialMouseMRINanoparticleNanoparticlesNeoplasmNon-HumanNuclear Magnetic Resonance ImagingPertuzumabpHPolypeptidePolypyrrolesPriority JournalProteinsSystemic DeliveriesTherapeutic EfficacyTherapeutic ModalityTissueTissue Activated Magnetic Resonance Imaging Contrast EnhancementToxicityTrastuzumabTumor-TargetingTumor Targeted ToxicityTumor TargetingTumorsUnclassified 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
  • Author Hwang, Jae Youn MBIS(Multimodal Biomedical Imaging and System) Laboratory
  • Research Interests Multimodal Imaging; High-Frequency Ultrasound Microbeam; Ultrasound Imaging and Analysis; 스마트 헬스케어
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Department of Information and Communication EngineeringMBIS(Multimodal Biomedical Imaging and System) Laboratory1. Journal Articles

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