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.
journal_name
Proc Natl Acad Sci U S Aauthors
Agadjanian H,Ma J,Rentsendorj A,Valluripalli V,Hwang JY,Mahammed A,Farkas DL,Gray HB,Gross Z,Medina-Kauwe LKdoi
10.1073/pnas.0901531106subject
Has Abstractpub_date
2009-04-14 00:00:00pages
6105-10issue
15eissn
0027-8424issn
1091-6490pii
0901531106journal_volume
106pub_type
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