TY - JOUR
T1 - A corrole nanobiologic elicits tissue-activated MRI contrast enhancement and tumor-targeted toxicity
AU - Sims, Jessica D.
AU - Hwang, Jae Youn
AU - Wagner, Shawn
AU - Alonso-Valenteen, Felix
AU - Hanson, Chris
AU - Taguiam, Jan Michael
AU - Polo, Richard
AU - Harutyunyan, Ira
AU - Karapetyan, Gevorg
AU - Sorasaenee, Karn
AU - Ibrahim, Ahmed
AU - Marban, Eduardo
AU - Moats, Rex
AU - Gray, Harry B.
AU - Gross, Zeev
AU - Medina-Kauwe, Lali K.
PY - 2015/11/10
Y1 - 2015/11/10
N2 - 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.
AB - 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.
KW - Corrole
KW - Manganese
KW - MRI
KW - Nanoparticle
KW - Tumor-targeting
UR - http://www.scopus.com/inward/record.url?scp=84940982858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940982858&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2015.08.046
DO - 10.1016/j.jconrel.2015.08.046
M3 - Article
C2 - 26334483
AN - SCOPUS:84940982858
SN - 0168-3659
VL - 217
SP - 92
EP - 101
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -