Tumor detection and elimination by a targeted gallium corrole.

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.

authors

Agadjanian H,Ma J,Rentsendorj A,Valluripalli V,Hwang JY,Mahammed A,Farkas DL,Gray HB,Gross Z,Medina-Kauwe LK

doi

10.1073/pnas.0901531106

subject

Has Abstract

pub_date

2009-04-14 00:00:00

pages

6105-10

issue

15

eissn

0027-8424

issn

1091-6490

pii

0901531106

journal_volume

106

pub_type

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