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A corrole nanobiologic elicits tissue-activated MRI contrast enhancement and tumor-targeted toxicity

Sims, Jessica D. and Hwang, Jae Youn and Wagner, Shawn and Alonso-Valenteen, Felix and Hanson, Chris and Taguiam, Jan Michael and Polo, Richard and Harutyunyan, Ira and Karapetyan, Gevorg and Sorasaenee, Karn and Ibrahim, Ahmed and Marban, Eduardo and Moats, Rex and Gray, Harry B. and Gross, Zeev and Medina-Kauwe, Lali K. (2015) A corrole nanobiologic elicits tissue-activated MRI contrast enhancement and tumor-targeted toxicity. Journal of Controlled Release, 217 . pp. 92-101. ISSN 0168-3659. PMCID PMC4623877. https://resolver.caltech.edu/CaltechAUTHORS:20150911-091604421

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.jconrel.2015.08.046DOIArticle
http://www.sciencedirect.com/science/article/pii/S0168365915300894PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623877PubMed CentralArticle
ORCID:
AuthorORCID
Sorasaenee, Karn0000-0002-3364-1918
Gray, Harry B.0000-0002-7937-7876
Additional Information:© 2015 Elsevier B.V. Received 23 April 2015; Received in revised form 10 August 2015; Accepted 24 August 2015; Available online 31 August 2015. This research was supported by grants to LKMK from the NIH/NCI (R01 CA140995 and R01 CA129822), and from the National Center for Research Resources, Grant UL1RR033176, which is now at the National Center for Advancing Translational Sciences, Grant UL1TR000124. The authors are grateful to IC Atanasov, X Zhang, LS Lam, and H Zhou at the Electron Imaging Center for NanoMachines (EICN) within the California NanoSystems Institute (CNSI) at UCLA for EMservices and assistance; and acknowledge the use of instruments within the EICN supported by the NIH(1S10RR23057 to ZHZ) and CNSI at UCLA. The authors also thank X Da and W Tawackoli of the Cedars-Sinai Imaging Core for Xenogen imaging services provided for this study. Finally, we thank the University of Wisconsin–Madison Biochemistry MediaLab for use of mouse clipart. JDS thanks A Rozenek and JR Sims for their support and inspiration; and LKMK thanks C Rey, MM-Kauwe, and D Revetto for unwavering support and guidance. ZG thanks the Israel Science Foundation (Grant No. 274/13) for financial support of work performed at the Technion. IH, GK, KS, RAM thank the Radiology Research Endowment Fund and the Small Animal Imaging Core at the Saban Research Instititute.
Funders:
Funding AgencyGrant Number
NIHR01 CA140995
NIHR01 CA129822
National Center for Research ResourcesUL1RR033176
National Center for Advancing Translational SciencesUL1TR000124
NIH1S10RR23057
Israel Science Foundation274/13
Saban Research InstitituteUNSPECIFIED
Subject Keywords:Nanoparticle; Tumor-targeting; Corrole; Manganese; MRI
PubMed Central ID:PMC4623877
Record Number:CaltechAUTHORS:20150911-091604421
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150911-091604421
Official Citation:Jessica D. Sims, Jae Youn Hwang, Shawn Wagner, Felix Alonso-Valenteen, Chris Hanson, Jan Michael Taguiam, Richard Polo, Ira Harutyunyan, Gevorg Karapetyan, Karn Sorasaenee, Ahmed Ibrahim, Eduardo Marban, Rex Moats, Harry B. Gray, Zeev Gross, Lali K. Medina-Kauwe, A corrole nanobiologic elicits tissue-activated MRI contrast enhancement and tumor-targeted toxicity, Journal of Controlled Release, Volume 217, 10 November 2015, Pages 92-101, ISSN 0168-3659, http://dx.doi.org/10.1016/j.jconrel.2015.08.046. (http://www.sciencedirect.com/science/article/pii/S0168365915300894)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:60184
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 Sep 2015 17:22
Last Modified:09 Mar 2020 13:19

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