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Tumor detection and elimination by a targeted gallium corrole

Agadjanian, Hasmik and Ma, Jun and Rentsendorj, Altan and Valluripalli, Vinod and Hwang, Jae Youn and Mahammed, Atif and Farkas, Daniel L. and Gray, Harry B. and Gross, Zeev and Medina-Kauwe, Lali K. (2009) Tumor detection and elimination by a targeted gallium corrole. Proceedings of the National Academy of Sciences of the United States of America, 106 (15). pp. 6105-6110. ISSN 0027-8424. PMCID PMC2669340. http://resolver.caltech.edu/CaltechAUTHORS:20090514-144240338

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Abstract

Sulfonated gallium(III) corroles are intensely fluorescent macrocyclic compounds that spontaneously assemble with carrier proteins to undergo cell entry. We report in vivo imaging and therapeutic efficacy of a tumor-targeted corrole noncovalently assembled with a heregulin-modified protein directed at the human epidermal growth factor receptor (HER). Systemic delivery of this protein-corrole complex results in tumor accumulation, which can be visualized in vivo owing to intensely red corrole fluorescence. Targeted delivery in vivo leads to tumor cell death while normal tissue is spared. These findings contrast with the effects of doxorubicin, which can elicit cardiac damage during therapy and required direct intratumoral injection to yield similar levels of tumor shrinkage compared with the systemically delivered corrole. The targeted complex ablated tumors at >5 times a lower dose than untargeted systemic doxorubicin, and the corrole did not damage heart tissue. Complexes remained intact in serum and the carrier protein elicited no detectable immunogenicity. The sulfonated gallium(III) corrole functions both for tumor detection and intervention with safety and targeting advantages over standard chemotherapeutic agents.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.0901531106DOIArticle
http://www.pnas.org/content/106/15/6105.abstractPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669340/PubMed CentralArticle
Additional Information:© 2009 by the National Academy of Sciences. Contributed by Harry B. Gray, February 15, 2009 (received for review December 18, 2008). We thank Krishnan Ramanujan for helpful feedback and critical review of this work; Kolja Wawrowsky (Cedars-Sinai Medical Center Confocal Core Facility) and Sarah Hamm-Alvarez and Jiansong Xie (University of Southern California Department of Pharmaceutical Sciences) for assistance with microscopic imaging; and Renata Stripecke and Emmanuelle Faure-Kumar (UCLA Vector Core) for provision of adenovirus and lentivirus vectors. This work was supported by National Institutes of Health (NIH) Grants R21 CA116014 and R01 CA102126, Department of Defense Grant BC050662, Susan G. Komen Breast Cancer Foundation Grant BCTR0201194, and a Donna and Jesse Garber Award (all to L.K.M.-K.), and by the U.S. Navy Bureau of Medicine and Surgery (D.L.F.). Work performed at the Technion-Israel Institute of Technology was supported by grants from the Gurwin and Binational Science foundations (to Z.G.). Research at California Institute of Technology was supported by grants from NIH and the National Science Foundation (to H.B.G.).
Funders:
Funding AgencyGrant Number
NIHR21 CA116014
NIHR01 CA102126
Department of DefenseBC050662
Susan G. Komen Breast Cancer FoundationBCTR0201194
Donna and Jesse Garber AwardUNSPECIFIED
Navy Bureau of Medicine and SurgeryUNSPECIFIED
Gurwin FoundationUNSPECIFIED
NSFUNSPECIFIED
Binational Science Foundation (USA-Israel)UNSPECIFIED
Subject Keywords:heregulin; human epidermal growth factor receptor; cancer; in vivo imaging; porphyrinoids
Issue or Number:15
PubMed Central ID:PMC2669340
Record Number:CaltechAUTHORS:20090514-144240338
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20090514-144240338
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14219
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:13 Aug 2009 22:14
Last Modified:26 May 2017 21:17

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